Control Over Controlled Radical Polymerization Processes

ABSTRACT

A procedure for improved temperature control in controlled radical polymerization processes is disclosed. The procedure is directed at controlling the concentration of the persistent radical in ATRP and NMP polymerizations procedures and the concentration of radicals in a RAFT polymerization process by feeding a reducing agent or radical precursor continuously or intermittently to the reaction medium through one of more ports.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/666,946, filed Mar. 24, 2015, which is further a continuation of U.S.patent application Ser. No. 14/459,871, filed Aug. 14, 2014, now U.S.Pat. No. 9,546,225, which is further a continuation of U.S. patentapplication Ser. No. 12/926,780, filed Dec. 8, 2010, now U.S. Pat. No.8,822,610, which is a continuation-in-part of U.S. patent applicationSer. No. 12/653,937, filed Dec. 18, 2009, now U.S. Pat. No. 8,815,971,which further claims the benefit of U.S. Provisional Application No.61/203,387, filed Dec. 22, 2008. The foregoing related applications, intheir entirety, are incorporated herein by reference.

TECHNICAL FIELD OF THE INVENTION

Three controlled radical polymerization (CRP) procedures are presentlybroadly utilized for the synthesis of high performance functionalmaterials. They are: atom transfer radical polymerization (ATRP)inclusive of ARGET ATRP (Activators ReGenerated by Electron Transfer forAtom Transfer Radical Polymerization) and/or ICAR ATRP (Initiators forContinuous Activator Regeneration for Atom Transfer RadicalPolymerization), reversible addition fragmentation transfer (RAFT) andnitroxide mediated polymerization (NMP). Procedures for improved levelsof control over various CRP processes for radically (co)polymerizablemonomers are disclosed. The improvements are focused on definingindustrially scalable procedures with reduced environmental impact forthe three CRP procedures. In the case of atom transfer radicalpolymerization (ATRP) the improved process is conducted in the presenceof low parts per million of a transition metal catalyst complex and ahigh degree of control is attained by running the reaction underconditions of controlled addition/activation of a reducing agent/radicalinitiator. In the case of RAFT overall control is improved by conductingthe reaction under conditions of controlled addition/activation of theradical initiator. The rate of polymerization in a nitroxide mediatedpolymerization (NMP) is controlled under conditions of controlledaddition/activation of a radical initiator to control the concentrationof the persistent radical.

BACKGROUND OF THE INVENTION

Many high-performance materials, particularly segmented copolymers orcomposite structures, require controlled synthesis of polymers fromfunctional monomers employing well defined initiators. [MacromolecularEngineering. Precise Synthesis, Materials Properties, Applications;Wiley-VCH: Weinheim, 2007.] For optimal performance in many applicationsthe materials also require controlled processing taking into account thesize and topology of phase separated domains and the dynamics of testingresponse rates.

Access to well-defined block copolymers was opened by Szwarc in the1950's [Nature 1956, 176, 1168-1169] by the development of livinganionic polymerization. The biggest limitation of this technique is itssensitivity to impurities (moisture, carbon dioxide) and even mildelectrophiles, which limits the process to a narrow range of monomers.The reaction medium and all components have to be extensively purifiedbefore polymerization, thus preparation of functional block copolymersor other well-defined polymeric materials in high purity can bechallenging. Nevertheless, anionic polymerization, which was firstimplemented in an academic setting, was quickly adapted on an industrialscale and ultimately led to the mass production of several well-definedblock copolymers, such as polystyrene-b-polybutadiene-b-polystyrene,performing as a thermoplastic elastomer. [Thermoplastic Elastomers, 3rdEd.; Hanser: Munich, 2004]

The fast industrial adaptation of such a challenging technique may beexplained by the fact that anionic polymerization was the first and,indeed only example of a living polymerization process for more thanthree decades, that allowed for the synthesis of previously inaccessiblewell defined high-performance materials from a very narrow selection ofvinyl monomers. Nevertheless materials based on modified blockcopolymers with properties that were desired in many applications, werethe main driving force for scaling up anionic polymerization processes.[Ionic Polymerization and Living Polymers; Chapman and Hall, New York,1993, ISBN 0-412-03661-4.]

In late 1970's to early 1990's, living carbocationic polymerization wasdiscovered and optimized. [Adv. Polym. Sci. 1980, 37, 1-144.] Howeverthis procedure is just as sensitive to impurities as anionicpolymerization and the range of polymerizable monomers for bothtechniques was essentially limited to non-polar vinyl monomers.

While many earlier attempts were made to develop controlled radicalpolymerization (CRP) processes the critical advances were made in themid 1990s. CRP can be applied to the polymerization of functionalmonomers and hence preparation of many different site specificfunctional (co)polymers under mild conditions became feasible.[Materials Today 2005, 8, 26-33 and Handbook of Radical Polymerization;Wiley Interscience: Hoboken, 2002.] From a commercial point of view, CRPprocesses can be conducted at convenient temperatures, do not requireextensive purification of the monomers or solvents and can be conductedin bulk, solution, aqueous suspension, emulsion, etc. CRP allows thepreparation of polymers with predetermined molecular weights, lowpolydispersity and controlled composition, and topology. Radicalpolymerization is much more tolerant of functional groups than ionicpolymerization processes and a broader range of unsaturated monomers canbe polymerized providing materials with site specific functionality. Inaddition, copolymerization reactions, which are generally challengingfor ionic polymerizations due to large differences in reactivity ratiosof monomers under ionic polymerization conditions, are easy to performusing radical based CRP. This provides an opportunity to synthesizepolymeric materials with predetermined molecular weight (MW), lowpolydispersity (PDI), controlled composition, site specificfunctionalities, selected chain topology and composite structures thatcan be employed to incorporate bio- or inorganic species into the finalproduct.

The three most studied, and commercially promising, methods ofcontrolling radical polymerization are nitroxide mediated polymerization(NMP), [Chemical Reviews 2001, 101, 3661-3688] atom transfer radicalpolymerization (ATRP), [J. Chem. Rev. 2001, 101, 2921-2990; Progress inPolymer Science 2007, 32, 93-146.] and degenerative transfer withdithioesters via reversible addition-fragmentation chain transferpolymerization (RAFT). [Progress in Polymer Science 2007, 32, 283-351]Each of these methods relies on establishment of a dynamic equilibriumbetween a low concentration of active propagating chains and apredominant amount of dormant chains that are unable to propagate orterminate as a means of extending the lifetime of the propagatingchains.

The simple four component atom transfer radical polymerization (ATRP)process, shown below in Scheme 1, was discovered by Matyjaszewski atCarnegie Mellon University and he and his coworkers have disclosed ATRP,and many improvements to the basic ATRP process which may be applicableto some or all of the embodiments herein, in a number of patents andpatent applications [U.S. Pat. Nos. 5,763,546; 5,807,937; 5,763,548,5,789,487; 5,945,491; 6,111,022; 6,121,371; 6,124,411; 6,162,882;6,624,262; 6,407,187; 6,512,060; 6,627,314; 6,790,919; 7,019,082;7,049,373; 7,064,166; 7,157,530 and U.S. patent application Ser. No.09/534,827; International Publication WO 2007/025310 A1 andInternational Application Nos. PCT/US2004/009905; PCT/US2005/007264;PCT/US2005/007265; PCT/US2006/033152, PCT/US2006/033792 andPCT/US2006/048656], all of which are herein incorporated by reference intheir entirety. Based on the number of publications, ATRP has emerged asthe preferred process for controlled/living polymerization of radically(co)polymerizable monomers. Typically, an ATRP process comprises use ofa transition metal complex that acts as a catalyst for the controlledpolymerization of radically (co)poiymerizabie monomers from an initiatorwith one or more transferable atoms or groups. Suitable initiators arefrequently substituted alkyl halides attached to a low molecular weightmolecule with an additional non-initiating functionality, a lowmolecular weight initiator or macroinitiator with two or moretransferable atoms or groups or a solid inorganic or organic materialwith tethered initiating groups. The transition metal catalystparticipates in a repetitive redox reaction whereby the lower oxidationstate transition metal complex (M_(t) ^(n)/Ligand) homolytically removesa transferable atom or group from an initiator molecule or dormantpolymer chain, P_(n)—X, to form the active propagating species, P^(●)_(n), in an activating reaction with a rate of activation k_(a) whichpropagates at a rate k_(p) before the higher oxidation state transitionmetal complex (X-M_(t) ^(n+1)/Ligand) deactivates the active propagatingspecies, P^(●) _(n), by donating back a transferable atom or group tothe active chain end, rate k_(da), not necessarily the same atom orgroup from the same transition metal complex (Scheme 1).

The catalyst is not bound to the chain end, as in coordinationpolymerization, and can therefore be used in a controlled/livingpolymerization process at sub-stoichiometric amounts relative to theinitiator. Nevertheless, as a consequence of radical-radical terminationreactions, proceeding with a rate=k_(t) in Scheme 1, forming P_(n)—P_(m)dead chains and an excess of X-M_(t) ^(n+1)/Ligand.

Examples of the spectrum of new well-defined polymeric materialsprepared using ATRP in the past decade include block copolymers,branched polymers, polymeric stars, brushes, and networks, each withpre-determinable site specific functionality as well as hybrids withinorganic materials or bio-conjugates. However, its widespreadcommercial utilization is still limited. [Chem. Rev. 2007, 107,2270-2299.] Nevertheless, these custom fabricated materials havepotential to improve the performance of a multitude of commercialproducts in the areas of personal care and cosmetics, detergents andsurfactants, paints, pigments and coatings, adhesives, thermoplasticelastomers, biocompatible materials and drug delivery systems if a costeffective, environmentally benign, scalable process can be defined.

The initially defined normal ATRP process requires a high catalystconcentration, often approaching 0.1 M in bulk monomer polymerizationreactions, typical concentrations range from 0.5% to 1 mol % vs.monomer, [Handbook of Radical Polymerization; Wiley Interscience:Hoboken, 2002] to overcome the effects of continuous buildup of ATRP'sequivalent of the persistent radical (X-M_(t) ^(n+1)/Ligand). [Journalof the American Chemical Society 1986, 108, 3925-3927 and Macromolecules1997, 30, 5666-5672.] The high levels of catalyst employed in theinitial ATRP reactions, even those involving more active catalystcomplexes, were required to overcome the effects of unavoidable increasein the concentration of the higher oxidation state catalyst due tounavoidable radical-radical termination reactions. Since the finalreactor product contained between 1,000 and 10,000 ppm of the transitionmetal complex, the resulting polymer has a strong color and could bemildly toxic. This level of catalyst has to be removed from the finalpolymer prior to use in most applications. The added production costsassociated with adsorption or extraction of the catalyst in addition toisolation and recycle of organic solvents have slowed industrialacceptance of ATRP to produce materials desired by the marketplace. Anadditional problem of industrial relevance involves the use of the morerecently developed highly active (i.e., very reducing) ATRP catalysts.Special handling procedures are often required to remove all oxygen andoxidants from these systems prior to addition of the rapidly oxidizablecatalyst complex. The energy used in these purification process(es)and/or the need of rigorously deoxygenated systems contributes to thegeneration of chemical waste and adds cost. These are the major factorswhich constrain the commercial application of ATRP.

Recent advances in ATRP by the present inventors in conjunction with oneof the inventors of ATRP, K. Matyjaszewski, has been disclosed inInternational Application No. PCT/US2006/048656, published as WO2007/075817, hereby incorporated in their entirety by reference andfurther including incorporation of references disclosed therein todefine the state of the art in ATRP and definitions for some of thelanguage used herein. In that application, it was disclosed that theconcentration of the catalyst used for an ATRP can be reduced to 1-100ppm by addition of a reducing agent, or a free radical initiator, thatacts throughout the reaction to continuously regenerate the loweroxidation state activator from accumulating higher oxidation statedeactivator, Scheme 2. Some suitable reducing agents listed inincorporated references include; sulfites, bisulfites, thiosulfites,mercaptans, hydroxylamines, amines, hydrazine (N₂H₄), phenylhydrazine(PhNHNH₂), hydrazones, hydroquinone, food preservatives, flavonoids,beta carotene, vitamin A, α-tocopherols, vitamin E, propyl gallate,octyl gallate, BHIA, BHT, propionic acids, ascorbic acid, sorbates,reducing sugars, sugars comprising an aldehyde group, glucose, lactose,fructose, dextrose, potassium tartrate, nitrites, nitrites, dextrin,aldehydes, glycine, and many antioxidants.

This improvement in ATRP was called ARGET ATRP because the Activator wascontinuously ReGenerated by Electron Transfer. In Scheme 2 theregeneration is conducted by addition of a reducing agent but thedeactivator can also be reduced by addition of a free radical initiatorin a process called ICAR (Initiators for Continuous ActivatorRegeneration) ATRP.

These novel initiation/catalyst reactivation procedures allow a decreasein the amount of catalyst needed to drive a controlled ATRP to highconversion from 10,000 ppm employed in classical ATRP to, in some cases,10 ppm or less where catalyst removal or recycling would be unwarrantedfor many industrial applications.

Furthermore ARGET/ICAR ATRP processes can start with the oxidativelystable, easy to handle and store Cu^(II) species, as it is reduced insitu to the Cu^(I) state. Furthermore, the level of control in thedisclosed ICAR/ARGET ATRP processes are essentially unaffected by anexcess (still small amount compared to initiator) of the reducing agentto continuously regenerate the lower oxidation state activator when/ifit is oxidized in the presence of limited amounts of air. [Langmuir2007, 23, 4528-4531.]

Chain-end functionality in a normal ATRP may be lost by a combination ofradical-radical termination reactions and by side reactions betweengrowing radicals and the catalyst complex; Cu^(I) (oxidation of radicalto carbocation) or Cu^(II) species (reduction of radical to carbanion).Therefore another important feature of the new ARGET/ICAR catalyticsystems is the suppression/reduction of side reactions due to the use ofa low concentration of the transition metal complex. Reducedcatalyst-based side reactions in ICAR and ARGET ATRP allow synthesis ofhigher molecular weight polymers and polymers with higher chain-endfunctionality which may allow the preparation of pure, certainly purer,block copolymers.

It was envisioned to be a simple robust procedure.

In application PCT/US2006/048656 the re-activator was added to thereaction in a single addition and control was exerted over the reactionby continuous adjustment of K_(ATRP) in the presence of excess reducingagent. Successful polymerization was achieved on the laboratory scale,10-50 mL Schlenk flasks, for common monomers such as methyl methacrylate(MMA), butyl acrylate (nBA), styrene (St) and acrylonitrile (AN). Thesuccessful synthesis of block copolymers from common monomers such asMMA, nBA, MA and St was reported.

The critical phrase in the above paragraph discloses the scale at whichthe innovative work to define the improved procedures was conducted:10-50 mL. When the procedures disclosed in PCT/US2006/048656 were scaledup some critical process disadvantages accompanying the improvementsmade in application became apparent:

a) slow reactions (especially for methacrylates, styrenes)

b) exothermic process (especially for acrylates) requiring

c) the need of precise temperature control

a) d) limited information for scale up and automation of process.

Procedures to overcome these limitations, particularly at larger scale,are disclosed herein. Indeed in one embodiment of the inventiondisclosed controlled radical polymerization processes where the rate ofaddition of a reducing agent/radical initiator is continuously adjustedallows conversion of monomer to polymer to exceed 80%, preferably exceed90% and optimally exceed 95%.

SUMMARY OF THE INVENTION

One embodiment of the polymerization processes of the present inventionare directed to polymerizing free radically polymerizable monomers inthe presence of a polymerization medium initially comprising at leastone transition metal catalyst, for example at a relatively lowconcentration, and an atom transfer radical polymerization initiator.The polymerization medium may additionally comprise a reducing agent ora radical initiator and/or ligand. Sufficient ligand may be added to thereaction medium to modify solubility and activity of the transitionmetal catalyst. The one or more reducing agents or radical initiatorsmay be added initially or during the polymerization process in acontinuous or intermittent manner or activated in an intermittentmanner. The polymerization process may further comprise reacting thereducing agent with at least one of the transition metal catalyst in anoxidized state further comprising a radically transferable atom or groupto form a compound that does not participate significantly in control ofthe polymerization process. A transition metal in the zero oxidationstate can be employed as a reducing agent.

Another embodiment of the disclosed process is directed towardscontinuous control over the concentration of the persistent radical in aNMP. In this embodiment the rate of decomposition of the initiator addedcontinuously or intermittently to the reaction is selected to match therate of radical/radical termination reactions that would otherwise buildup the concentration of the stable free radical and reduce the rate ofpropagation.

A further embodiment of the disclosed process concerns RAFTpolymerizations. In a RAFT polymerization the rate of polymerization iscontrolled by the rate of decomposition of the added initiator. Normallyall of the initiator is added to the reaction at the beginning of thereaction and this could lead to an increased rate of initiatordecomposition if the temperature of the reaction is not well controlledthroughout the polymerization vessel during each stage of the reaction.As noted for ICAR ATRP continuous addition of the initiator andmonitoring of the temperature of the reaction provides information on,if and when addition of the initiator should be stopped in order toretain control over the reaction.

Embodiments of the polymerization process of the present inventioninclude bulk polymerization processes, polymerization processesperformed in a solvent, polymerization processes conducted from solidsurfaces, biphasic polymerization process including emulsionpolymerization processes, mini-emulsion polymerization processes,microemulsion processes, reverse emulsion polymerization processes, andsuspension polymerization processes. In such biphasic polymerizationprocesses the polymerization processes may further comprise at least oneof a suspending medium, a surfactant or reactive surfactant, and amonomer phase comprising at least a portion of the radicallypolymerizable monomers.

It must be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “and,” and “the” include pluralreferents unless the context clearly dictates otherwise. Thus, forexample, reference to “a polymer” may include more than one polymer orcopolymers.

This disclosed procedures provide a means to optimize and automate thepolymerization processes by exercising continuous control over the ratioof activator/deactivator, concentration of persistent radical orconcentration of initiator present in a CRP.

The advantages of the disclosed ‘starve feeding/activation’ methodinclude:

-   -   a) use of lower amounts of catalyst and radical initiator or        reducing agent,    -   b) reduced need for precise temperature control,    -   c) higher reaction temperature, which allows higher conversions        in a shorter time with reduced amounts of solvents,    -   d) the potential for automation of the whole process, and    -   e) the development of safe scalable processes for exothermic        polymerization reactions, although heat removal is still a        requirement.

The resulting expansion of the utilization of the proposed system forCRP will allow a reduced cost for purification of the products, asignificant decrease in waste and improve safety by providing anadditional means to control reaction temperature. Furthermore the rateof addition of a reducing agent/radical initiator can be continuouslyadjusted to allow the conversion of monomer to polymer to exceed 80%,preferably exceed 90% and optimally exceed 95% by taking intoconsideration the viscosity of the reaction medium and the rate ofdiffusion of the added reducing agent.

In the following examples, and discussion of examples, ATRP is employedas an exemplary CRP but the disclosed procedures, components, and rangesmay be applied to NMP and RAFT as indicated above.

In one embodiment, a method for safely operating a fast large-scale ICARATRP polymerization process is provided, comprising: (a) mixing anunsaturated monomer, an initiator, and a metal catalyst; (b) adding anon-activated reducing agent (inclusive of, for example, athermo-activated or photo-activated reducing agent); (c) maintaining thepolymerization process at or above a temperature wherein thenon-activated reducing agent has a activation-dependent (for example,temperature or electromagnetic activation) t_(1/2) value of between 30sec. and 30 min. and optionally ligand.

In another embodiment, a method of polymerizing unsaturated monomers isprovided, comprising: (a) mixing unsaturated monomers with an inactivemetal catalyst, an initiator having a transferable atom and optionallyligand, wherein the inactive metal catalyst is present in the mixture atan amount of less than 250 ppm, on a mass basis relative to the totalmixture; (b) heating the mixture to a reaction temperature; (c) adding afirst portion of a non-activated reducing agent to the system togenerate an activated reducing agent, wherein the non-activated reducingagent has a decomposition activation dependent t_(1/2) value of between30 sec. and 30 min. at the reaction conditions (for example, temperatureor electromagnetic energy value); (d) reducing the inactive metalcatalyst with the activated reducing agent to form an active metalcatalyst; (e) transferring the transferable atom with the active metalcatalyst, thereby activating the initiator for unsaturated monomeraddition; and (f) adding at least a further portion of the non-activatedreducing agent to the mixture to induce further polymerization of theunsaturated monomer; wherein the at least further portion is added tothe mixture at a point where at least 10, 20 or 30 molar %, relative tothe amount of unsaturated monomer introduced into the mixture, has beenpolymerized, and wherein at least one polymer product has a degree ofpolymerization, with respect to the monomer residues corresponding tothe unsaturated monomer, of at least 10, 15, 20 or 25 and the overallmixture has a conversion of at least 60 molar % relative to the amountof unsaturated monomer introduced into the mixture.

In another embodiment, a method of radical polymerization of anunsaturated monomer is provided, comprising: (a) polymerizing anunsaturated monomer in a system comprising an initiator, optionallyligand and a metal catalyst at or above a reaction temperature; (b)adding at a controlled rate a first amount of non-activated reducingagent to the system; and (c) controlling the rate of polymerization ofthe unsaturated monomer by adding at a controlled rate a further amountof the non-activated reducing agent to the system at a point where atleast 10, 20 or 30 molar %, relative to the amount of unsaturatedmonomer introduced into the system, has been polymerized; wherein thereaction conditions are sufficient to activate the non-activatedreducing agent.

In certain embodiments, the initiator utilized in the method maycomprise a halide-substituted alkyl initiator.

In certain embodiments, the metal catalyst utilized in the method maycomprise an inactive metal-halide catalyst.

In certain embodiments, the metal catalyst utilized in the method maycomprise an active metal-halide catalyst.

In another embodiment, a method of making a polymer is provided,comprising: (a) preparing a reaction mixture comprising aradically-polymerizable unsaturated monomer, an initiator, optionallyligand and an inactive metal catalyst in a molar ratio of theunsaturated monomer to the initiator of 25-5000:1 and a molar ratio ofthe catalyst to the initiator of 0.001 to 0.5:1; and/or where the metalcatalyst is present in the mixture at an amount of less than 250 ppm, ona mass basis relative to the total mixture; (b) heating the reactionmixture to a first temperature; (c) disbursing a portion of anon-activated reducing agents (e.g., thermo-activated reducing agent)into the heated reaction mixture; (d) allowing a quantity of saidportion of the non-activated reducing agent to decompose to an activatedreducing agent; (e) reducing a portion of the inactive metal catalystwith a portion of the activated reducing agent to form at least oneactive metal catalyst; (f) activating one or more of the initiators withthe at least one active metal catalyst to form one or more activatedinitiators; (g) polymerizing at least one monomer in the presence of oneor more activated initiators to extend a polymer chain; and (h)repeating steps (c)-(g) while maintaining the reaction conditions at orabove a the point that triggers the non-activated reducing agent todecompose to form an intiator at an activation-dependent t/2 value ofbetween 30 sec. and 30 min. In certain embodiments, the method steps(c)-(h) may be conducted substantially continuously for a period of atleast 2 hours and the non-activated reducing agent may be introduced ina steady, continuous, dis-continuous, varying, gradient, variable,increasing, decreasing, increasing follow-by decreasing, decreasingfollowed by increasing and/or combinations of these techniques.

In certain embodiments, the non-activated reducing agent (may be forexample a thermo-activated reducing agent and/or a photo-activatedreducing agent) utilized in the method may be continuously disbursedinto the heated reaction mixture and the portion may be adjustedperiodically over the course of the polymerization reaction, relative tothe molar conversion of unsaturated monomer.

In certain embodiments, the non-activated reducing agent (may be forexample a thermo-activated reducing agent and/or a photo-activatedreducing agent) utilized in the method may be continuously disbursedinto the heated reaction mixture and the portion is adjustedperiodically over the time course of the polymerization reaction,relative to the process parameters of temperature and viscosity.

In certain embodiments, the non-activated reducing agent (may be forexample a thermo-activated reducing agent and/or a photo-activatedreducing agent) utilized in the method may be continuously disbursedinto the heated reaction mixture and the portion is adjustedperiodically over the course of the polymerization reaction, relative tothe molar conversion of unsaturated monomer, over an interval of time,wherein the interval of time is greater than three minutes.

In certain embodiments, the non-activated reducing agent utilized in themethod may not be added until at least 15, 30, 45 or 60 molar %conversion of the unsaturated monomer is achieved, relative to the molaramount of unsaturated monomer.

In certain embodiments, the second temperature utilized in the methodmay be at least 10 degrees, for example 12 or 15 degrees hotter thansaid first temperature.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

The following figures exemplify aspects of the disclosed process but donot limit the scope of the process to the examples discussed.

FIG. 1. Variation of temperature inside a 1 L batch reactor during ARGETATRP of nBA. Experimental conditions:nBA/DEBMM/CuBr₂/TPMA/Sn(EH)₂=500/1/0.025/0.1/0.1, in bulk at 60° C.

FIG. 2. Parameters employed for the computer simulation of thepolymerization of MMA under a series of reaction conditions. Thepurpose: to find optimal conditions for new feeding method. Results:models were built and successful simulations were performed and optimalconditions for the particular embodiment were found. Concerns: heattransfer, side reactions, catalyst stability, etc. not taken intoaccount.

FIGS. 3A-3C. The results for the very first computer simulation for thenew ‘feeding’ method for an ICAR ATRP of MMA, wherein:

FIG. 3 A is a kinetic plot;

FIG. 3 B shows the increase in molecular weight and decrease in PDI vs.conversion; and

FIG. 3 C is a GPC trace. All simulations done for experimentalconditions: MMA/DEBMM/Cu^(II)Br₂/TPMA/AIBN=500/1/0.025/0.025/0.05 inbulk at 90° C., feeding time 10 h.

FIG. 4 A. Molecular weight and PDI vs. conversion for comparativeexample C1.

FIG. 4 B. GPC curves for comparative example C1.

FIG. 5 A. Molecular weight and PDI vs. conversion for comparativeexample C2.

FIG. 5 B. GPC traces for comparative example C2.

FIG. 6 A. Molecular weight and PDI vs. conversion for comparativeexample C3.

FIG. 6 B. GPC curves for comparative example C3.

FIG. 7 A. Molecular weight and PDI vs. conversion for comparativeexample C4.

FIG. 7 B. GPC curves for comparative example C4.

FIG. 8 A. Kinetic plot for comparative example C5.

FIG. 8 B. Molecular weight and PDI vs. conversion for comparativeexample C5.

FIG. 8 C. GPC curves for comparative example C5.

FIG. 8 D. Temperature profile for comparative example C5.

FIGS. 9A-9C. Polymerization of MMA targeting low degree ofpolymerization, wherein:

FIG. 9A is a kinetic plot;

FIG. 9B shows molecular weight and PDI vs. conversion; and

FIG. 9C are GPC traces for ICAR ATRP of MMA with feeding of AIBN(experiment 08-006-165). Conditions:MMA/DEBMM/CuBr₂/TPMA/AIBN=100/1/0.005/0.025/−; in bulk [MMA]=8.9 mol/L,50 ppm of Cu, T=90° C. Feeding rate slow: 0.002 mol equivalent of AIBNvs. DEBMM in 1 h (AIBN in 40 ml of solvent to 850 ml of the reactionsolution).

FIGS. 10A-10C. Polymerization of MMA targeting high degree ofpolymerization, wherein:

FIG. 10 A is a kinetic plot;

FIG. 10 B shows molecular weight and PDI vs. conversion; and

FIG. 10 C is a GPC trace for ICAR ATRP of MMA with feeding of V-70(experiment 08-006-180). Conditions:MMA/DEBMM/CuBr₂/TPMA/V-70=1000/1/0.05/0.1/−; in bulk [MMA]=8.9 mol/L, 50ppm of Cu, T=80° C. Feeding rate slow: 0.004 mol equivalent of V-70 vs.DEBMM in 1 h (V-70 in 40 ml of solvent to 850 ml of the reactionsolution).

FIGS. 11A-11F. Computer simulation of polymerization of n-butylacrylate, specifically:

FIGS. 11 A-C with the feeding of AIBN, wherein:

FIG. 11A is the kinetic plot;

FIG. 11B is the molecular weight and PDI vs. conversion; and

FIG. 11C are GPC traces. Conditions for ICAR ATRP of nBA with feeding ofAIBN: nBA/DEBMM/CuBr₂/TPMA/AIBN=100/1/0.005/0.005/−; in bulk [nBA]=7.0mol/L, 50 ppm of Cu, T=90° C. Feeding rate fast: 0.03 mol equivalent ofAIBN vs. DEBMM in 6 h (AIBN in 90 ml of solvent to 1 L of the reactionsolution). Comments: simulated polymerization reached 99.2% conversionin 1.7 h (PDI=1.13; chain-end functionality=99%); there is a shortindication period but reaction was very fast and well controlled; amountof AIBN added after 1.7 h was 0.0086 mol equivalents vs. initiator; and

FIGS. 11 D-F without the feeding of AIBN, wherein:

FIG. 11D is the kinetic plot;

FIG. 11E is the molecular weight and PDI vs. conversion; and

FIG. 11F are GPC traces. Conditions for ICAR ATRP of nBA without feedingof AIBN: nBA/DEBMM/CuBr₂/TPMA/AIBN=100/1/0.005/0.005/0.03; in bulk[nBA]=7.0 mol/L, 50 ppm of Cu, T=90° C. Comments: simulatedpolymerization reached 99.2% conversion in 28 minutes (PDI=1.38;chain-end functionality=99%); polymerization was extremely fast andresultet in polymer with relatively broad molecular weight distribution(PDI=1.6-2.2 for lower conversions).

FIG. 12 A. Kinetic plot for example 2A.

FIG. 12 B. Molecular weight and PDI vs. conversion for example 2A.

FIG. 12 C. GPC curves for example 2A.

FIG. 12 D. Temperature profile for example 2A.

FIGS. 13A-13C. ICAR Polymerization of nBA using V-70 for ICAR ATRP ofnBA with feeding of V-70 (experiment WJ-08-0006-194), wherein:

FIG. 13A is the kinetic plot for example 2B;

FIG. 13B is the molecular weight and PDI vs. conversion for example 2B;and

FIG. 13C are GPC traces for example 2B. Conditions:nBA/DEBMM/CuBr₂/TPMA/V-70=1000/1/0.05/0.1/−; in bulk [nBA]=6.67 mol/L,50 ppm of Cu, T=70° C. Feeding rate slow: 0.002 mol equivalent of V-70vs. DEBMM in 1 h (V-70 in 40 ml of solvent to 850 ml of the reactionsolution).

FIG. 14. Temperature profile for run WJ-08-006-194 (example 2B).

FIGS. 15A-15C. ICAR polymerization of styrene (for WJ-08-006-194),wherein:

FIG. 15 A is a kinetic plot;

FIG. 15 B shows molecular weight and PDI vs. conversion; and

FIG. 15 C are GPC traces for ICAR ATRP of St with feeding of AIBN(experiment WJ-08-006-192). Conditions:St/DEBMM/CuBr₂/TPMA/AIBN=100/1/0.005/0.1/0.005; in bulk [St]=8.31 mol/L,50 ppm of Cu, T=100° C. Feeding rate slow: 0.008 mol equivalent of AIBNvs. DEBMM in 1 h (AIBN in 40 ml of solvent to 850 ml of the reactionsolution).

FIGS. 16A and 16B. Polymerization of St (high DP)—(experimentWJ-08-006-193). Automation of process, wherein:

FIG. 16A is a kinetic plot; and

FIG. 16B is the temperature profile. ICAR ATRP of St with feeding ofAIBN (experiment WJ-08-006-193). Conditions:St/DEBMM/CuBr₂/TPMA/AIBN=1000/1/0.05/0.15/0.025; in bulk [St]=8.31mol/L, 50 ppm of Cu, T=100-110° C. Feeding rate slow: 0.008 molequivalent of AIBN vs. DEBMM in 1 h (AIBN in 40 ml of solvent to 850 mlof the reaction solution).

FIGS. 17A and 17B. Kinetics for ICAR ATRP of St with feeding of AIBN(experiment WJ-08-006-193) targeting high DP, wherein:

FIG. 17A is the molecular weight and PDI vs. conversion; and

FIG. 17B are GPC traces. Conditions:St/DEBMM/CuBr₂/TPMA/AIBN=1000/1/0.05/0.15/0.025; in bulk [St]=8.31mol/L, 50 ppm of Cu, T=100-110° C. Feeding rate slow: 0.008 molequivalent of AIBN vs. DEBMM in 1 h (AIBN in 40 ml of solvent to 850 mlof the reaction solution).

DESCRIPTION OF THE EMBODIMENTS OF THE INVENTION

The term “hydrophilic” is understood to mean, in relation to a material,such as a polymeric arm, or a polymeric segment of a polymeric arm, thatthe material is water soluble and comprises hydrophilic segments havingan HLB equal to or greater than 8, for example, an HLB equal to 16-20,or equal to or greater than 18, 19, or 19.5. In certain embodiments, thehydrophilic segment may comprise at least 75 mol % of water-solublemonomer residues, for example, between 80 mol % to 100 mol % or at least85 mol %, 90 mol %, 95 mol %, or at least 97 mol % water-soluble monomerresidues.

The term “hydrophobic” is understood to mean, in relation to a material,such as a polymeric arm, or a polymeric segment of a polymeric arm, thatthe material is water insoluble and comprises hydrophilic segmentshaving an HLB less than 8, for example, an HLB less than 7. In certainembodiments, the hydrophobic segment may comprise at least 75 mol % ofwater-insoluble monomer residues, for example, between 80 mol % to 100mol % or at least 85 mol %, 90 mol %, 95 mol %, or at least 97 mol %water-insoluble monomer residues.

The term “monomer residue” or “monomeric residue” is understood to meanthe residue resulting from the polymerization of the correspondingunsaturated monomer. For example, a polymer derived from thepolymerization of an acrylic acid monomer (or derivatives thereof, suchas acid protected derivatives of acrylic acid including but not limitedto methyl ester or t-butyl ester of acrylic acid), will providepolymeric segments, identified as PAA, comprising repeat units ofmonomeric residues of acrylic acid, i.e., “—CH(CO₂H)CH₂—”. For example,a polymer derived from the polymerization of styrene monomers willprovide polymeric segments, identified as PS, comprising repeat units ofmonomeric residues of styrene, i.e., “—CH(C₆H₅)CH₂—.” For example, apolymer derived from the polymerization of monomeric divinylbenzenemonomers will provide polymeric segments comprising repeat units ofmonomeric residues of divinylbenzene, i.e., “—CH₂CH(C₆H₅)CHCH₂—.”

Suitable unsaturated monomers that may be useful in the reactions and/orformation of the (co)polymers, in the various embodiments presented anddisclosed in this application, may include but are not limited to, thoseselected from protected and unprotected acrylic acid; such asmethacrylic acid; ethacrylic acid; methyl acrylate; ethyl acrylate;n-butyl acrylate; iso-butyl acrylate; t-butyl acrylate; 2-ethylhexylacrylate; decyl acrylate; octyl acrylate; methyl methacrylate; ethylmethacrylate; n-butyl methacrylate; iso-butyl methacrylate; t-butylmethacrylate; 2-ethylhexyl methacrylate; decyl methacrylate; methylethacrylate; ethyl ethacrylate; n-butyl ethacrylate; iso-butylethacrylate; t-butyl ethacrylate; 2-ethylhexyl ethacrylate; decylethacrylate; 2,3-dihydroxypropyl acrylate; 2,3-dihydroxypropylmethacrylate; 2-hydroxyethyl acrylate; 2-hydroxypropyl acrylate;hydroxypropyl methacrylate; glyceryl monoacrylate; glycerylmonoethacrylate; glycidyl methacrylate; glycidyl acrylate; acrylamide;methacrylamide; ethacrylamide; N-methyl acrylamide; N,N-dimethylacrylamide; N,N-dimethyl methacrylamide; N-ethyl acrylamide; N-isopropylacrylamide; N-butyl acrylamide; N-t-butyl acrylamide; N,N-di-n-butylacrylamide; N,N-diethylacrylamide; N-octyl acrylamide; N-octadecylacrylamide; N,N-diethylacrylamide; N-phenyl acrylamide; N-methylmethacrylamide; N-ethyl methacrylamide; N-dodecyl methacrylamide;N,N-dimethylaminoethyl acrylamide; quaternised N,N-dimethylaminoethylacrylamide; N,N-dimethylaminoethyl methacrylamide; quaternisedN,N-dimethylaminoethyl methacrylamide; N,N-dimethylaminoethyl acrylate;N,N-dimethylaminoethyl methacrylate; quaternised N,N-dimethyl-aminoethylacrylate; quaternised N,N-dimethylaminoethyl methacrylate;2-hydroxyethyl acrylate; 2-hydroxyethyl methacrylate; 2-hydroxyethylethacrylate; glyceryl acrylate; 2-methoxyethyl acrylate; 2-methoxyethylmethacrylate; 2-methoxyethyl ethacrylate; 2-ethoxyethyl acrylate;2-ethoxyethyl methacrylate; 2-ethoxyethyl ethacrylate; maleic acid;maleic anhydride and its half esters; fumaric acid; itaconic acid;itaconic anhydride and its half esters; crotonic acid; angelic acid;diallyldimethyl ammonium chloride; vinyl pyrrolidone; vinyl imidazole;methyl vinyl ether; methyl vinyl ketone; maleimide; vinyl pyridine;vinyl pyridine-N-oxide; vinyl furan; styrene sulphonic acid and itssalts; allyl alcohol; allyl citrate; allyl tartrate; vinyl acetate;vinyl alcohol; vinyl caprolactam; vinyl acetamide; vinyl formamide;acrylonitrile; and mixtures thereof.

Other suitable unsaturated monomers that may be useful in the reactionsand/or formation of the (co)polymers, in the various embodimentspresented and disclosed in this application, may include but are notlimited to, those selected from methyl acrylate; methyl methacrylate;methyl ethacrylate; ethyl acrylate; ethyl methacrylate; ethylethacrylate; n-butyl acrylate; n-butyl methacrylate; n-butylethacrylate; 2-ethylhexyl acrylate; 2-ethylhexyl methacrylate;2-ethylhexyl ethacrylate; N-octyl acrylamide; 2-methoxyethyl acrylate;2-hydroxyethyl acrylate; N,N-dimethylaminoethyl acrylate;N,N-dimethylaminoethyl methacrylate; acrylic acid; methacrylic acid;N-t-butylacrylamide; N-sec-butylacrylamide; N,N-dimethylacrylamide;N,N-dibutylacrylamide; N,N-dihydroxyethyllacrylamide; 2-hydroxyethylacrylate, 2-hydroxyethyl methacrylate; benzyl acrylate;4-butoxycarbonylphenyl acrylate; butyl acrylate; 4-cyanobutyl acrylate;cyclohexyl acrylate; dodecyl acrylate; 2-ethylhexyl acrylate; heptylacrylate; iso-butyl acrylate; 3-methoxybutyl acrylate; 3-methoxypropylacrylate; methyl acrylate; N-butyl acrylamide; N,N-dibutyl acrylamide;ethyl acrylate; methoxyethyl acrylate; hydroxyethyl acrylate;diethyleneglycolethyl acrylate; acrylonitrile; styrene (optionallysubstituted with one or more C₁-C₁₂ straight or branched chain alkylgroups); alpha-methylstyrene; t-butylstyrene; p-methylstyrene; andmixtures thereof.

Suitable hydrophobic unsaturated monomers that may be useful in thereactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, that may beused includes, but is not limited to methyl acrylate; ethyl acrylate;n-butyl acrylate; iso-butyl acrylate; t-butyl acrylate; 2-ethylhexylacrylate; decyl acrylate; octyl acrylate; methyl methacrylate; ethylmethacrylate; n-butyl methacrylate; iso-butyl methacrylate; t-butylmethacrylate; 2-ethylhexyl methacrylate; decyl methacrylate; methylethacrylate; ethyl ethacrylate; n-butyl ethacrylate; iso-butylethacrylate; t-butyl ethacrylate; 2-ethylhexyl ethacrylate; decylethacrylate; 2,3-dihydroxypropyl acrylate; 2,3-dihydroxypropylmethacrylate; 2-hydroxypropyl acrylate; hydroxypropyl methacrylate;glycidyl methacrylate; glycidyl acrylate; acrylamides; styrene; styreneoptionally substituted with one or more C₁-C₁₂ straight or branchedchain alkyl groups; or alkylacrylate. For example, the hydrophobicmonomer may comprise styrene; α-methylstyrene; t-butylstyrene;p-methylstyrene; methyl methacrylate; or t-butyl-acrylate. For example,the hydrophobic monomer may comprise styrene. In certain embodiments,the hydrophobic monomer may comprise a protected functional group.

Suitable hydrophilic unsaturated monomers that may be useful in thereactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, that may beused includes, but is not limited to, protected and unprotected acrylicacid, such as methacrylic acid, ethacrylic acid; methyl acrylate; ethylacrylate; n-butyl acrylate; iso-butyl acrylate; t-butyl acrylate;2-ethylhexyl acrylate; decyl acrylate; octyl acrylate; methylmethacrylate; ethyl methacrylate; n-butyl methacrylate; iso-butylmethacrylate; t-butyl methacrylate; 2-ethylhexyl methacrylate; decylmethacrylate; methyl ethacrylate; ethyl ethacrylate; n-butylethacrylate; iso-butyl ethacrylate; t-butyl ethacrylate; 2-ethylhexylethacrylate; decyl ethacrylate; 2,3-dihydroxypropyl acrylate;2,3-dihydroxypropyl methacrylate; 2-hydroxyethyl acrylate;2-hydroxypropyl acrylate; hydroxypropyl methacrylate; glycerylmonoacrylate; glyceryl monoethacrylate; glycidyl methacrylate; glycidylacrylate; acrylamide; methacrylamide; ethacrylamide; N-methylacrylamide; N,N-dimethyl acrylamide; N,N-dimethyl methacrylamide;N-ethyl acrylamide; N-isopropyl acrylamide; N-butyl acrylamide;N-t-butyl acrylamide; N,N-di-n-butyl acrylamide; N,N-diethylacrylamide;N-octyl acrylamide; N-octadecyl acrylamide; N,N-diethylacrylamide;N-phenyl acrylamide; N-methyl methacrylamide; N-ethyl methacrylamide;N-dodecyl methacrylamide; N,N-dimethylaminoethyl acrylamide; quaternisedN,N-dimethylaminoethyl acrylamide; N,N-dimethylaminoethylmethacrylamide; quaternised N,N-dimethylaminoethyl methacrylamide;N,N-dimethylaminoethyl acrylate; N,N-dimethylaminoethyl methacrylate;quaternised N,N-dimethyl-aminoethyl acrylate; quaternisedN,N-dimethylaminoethyl methacrylate; 2-hydroxyethyl acrylate;2-hydroxyethyl methacrylate; 2-hydroxyethyl ethacrylate; glycerylacrylate; 2-methoxyethyl acrylate; 2-methoxyethyl methacrylate;2-methoxyethyl ethacrylate; 2-ethoxyethyl acrylate; 2-ethoxyethylmethacrylate; 2-ethoxyethyl ethacrylate; maleic acid; maleic anhydrideand its half esters; fumaric acid; itaconic acid; itaconic anhydride andits half esters; crotonic acid; angelic acid; diallyldimethyl ammoniumchloride; vinyl pyrrolidone vinyl imidazole; methyl vinyl ether; methylvinyl ketone; maleimide; vinyl pyridine; vinyl pyridine-N-oxide; vinylfuran; styrene sulphonic acid and its salts; allyl alcohol; allylcitrate; allyl tartrate; vinyl acetate; vinyl alcohol; vinylcaprolactam; vinyl acetamide; or vinyl formamide. For example, thehydrophilic unsaturated monomer may comprise protected and unprotectedacrylic acid, such as methacrylic acid, ethacrylic acid; methylacrylate; ethyl acrylate; n-butyl acrylate; iso-butyl acrylate; t-butylacrylate; 2-ethylhexyl acrylate; decyl acrylate; octyl acrylate; methylacrylate; methyl methacrylate; methyl ethacrylate; ethyl acrylate; ethylmethacrylate; ethyl ethacrylate; n-butyl acrylate; n-butyl methacrylate;n-butyl ethacrylate; 2-ethylhexyl acrylate; 2-ethylhexyl methacrylate;2-ethylhexyl ethacrylate; N-octyl acrylamide; 2-methoxyethyl acrylate;2-hydroxyethyl acrylate; N,N-dimethylaminoethyl acrylate;N,N-dimethylaminoethyl methacrylate; acrylic acid; methacrylic acid;N-t-butylacrylamide; N-sec-butylacrylamide; N,N-dimethylacrylamide;N,N-dibutylacrylamide; N,N-dihydroxyethyllacrylamide; 2-hydroxyethylacrylate; 2-hydroxyethyl methacrylate; benzyl acrylate;4-butoxycarbonylphenyl acrylate; butyl acrylate; 4-cyanobutyl acrylate;cyclohexyl acrylate; dodecyl acrylate; 2-ethylhexyl acrylate; heptylacrylate; iso-butyl acrylate; 3-methoxybutyl acrylate; 3-methoxypropylacrylate; methyl acrylate; N-butyl acrylamide; N,N-dibutyl acrylamide;ethyl acrylate; methoxyethyl acrylate; hydroxyethyl acrylate; ordiethyleneglycolethyl acrylate. For example, the hydrophilic unsaturatedmonomer may comprise protected and unprotected acrylic acid, such asmethacrylic acid, ethacrylic acid; methyl acrylate; ethyl acrylate;n-butyl acrylate; iso-butyl acrylate; t-butyl acrylate; 2-ethylhexylacrylate; decyl acrylate; octyl acrylate; 2-hydroxyethyl acrylate;N-isopropylacrylamide; ethylene glycol methacrylate; (polyethyleneglycol) methacrylate; or quaternized dimethylaminoethyl methacrylate.For example, the hydrophilic unsaturated monomer may comprise acrylicacid, such as methacrylic acid, 2-hydroxyethyl acrylate; acrylamide;vinyl pyrrolidone; vinyl pyridine; styrene sulphonic acid;PEG-methacrylate; 2-(dimethylamino)ethyl methacrylate;2-(trimethylamino)ethyl methacrylate; 2-acrylamido-2-methylpropanesulphonic acid. For example, the hydrophilic monomer may compriseacrylic acid.

Suitable metal catalysts that may be useful in the reactions and/orformation of the (co)polymers, in the various embodiments presented anddisclosed in this application, may include metals such as transitionmetals, like Cu⁰, that may convert to an oxided metal in situ and/orthose represented by Formula (I):

M_(t) ^(+n)X′_(n)  Formula (I)

wherein M_(t) ^(+n) may comprise Cu⁺¹; Cu⁺²; Fe⁺²; Fe⁺³; Ru⁺²; Ru⁺³;Cr⁺²; Cr⁺³; Mo⁺²; Mo⁺³; W⁺²; W⁺³; Mn⁺³; Mn⁺⁴; Rh⁺³; Rh⁺⁴; Re⁺²; Re⁺³;Co⁺¹; Co⁺²; V⁺²; V⁺³; Zn⁺¹; Zn⁺²; Au⁺¹; Au⁺²; Ag⁺¹; and Ag⁺²;

wherein X′ may comprise halogen; C₁-C₆-alkoxy; (SO₄)_(1/2); (PO₄)_(1/3);(R¹PO₄)_(1/2); (R¹ ₂ PO₄); triflate; hexafluorophosphate;methanesulfonate; arylsulfonate; CN; and R²CO₂; wherein R¹ may comprisearyl or a straight or branched C₁-C₂₀ alkyl group, such as C₁-C₁₀ alkylgroup, or where two R¹ groups may be joined to form a 5-, 6-, or7-membered heterocyclic ring; wherein R² may comprise hydrogen or astraight or branched C₁-C₆ alkyl group which may be substituted from 1to 5 times with a halogen; and

wherein n is the formal charge on the metal (0≤n≤7).

The metal catalyst may be a metal-halide catalyst, wherein themetal-halide catalyst may be present in an active form or in an inactiveform. For example, an inactive metal-halide catalyst may comprise ametal having a higher oxidation state than a metal of a correspondingactivate metal-halide catalyst. The inactive metal-halide catalyst maybe thought of as a pre-cursor form of an active metal-halide catalyst.

Suitable inactive metal-halide catalysts that may be useful in thereactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may include,but are not limited to, those comprising transitions metals, such as,copper, iron, and ruthenium, and one or more halides, such as chloride,bromide, iodide, or combinations thereof. For example, the inactivemetal-halide catalyst may be copper(II) halide, such as copper(II)chloride, copper(II) bromide, or copper(II) iodide.

Suitable active metal-halide catalysts that may be useful in thereactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may include,but are not limited to, those comprising transition metals, such as,copper, iron, and ruthenium, and one or more halides, such as chloride,bromide, iodide, or combinations thereof. For example, the activemetal-halide catalyst may be copper(I) halide, such as copper(I)chloride, copper(I) bromide, or copper(I) iodide.

For example, an inactive metal-halide catalyst, such as copper(II)bromide, may participate in a repetitive redox reaction to form anactive metal-halide catalyst, such as copper(I) bromide, whereby theactive metal-halide catalyst, optionally comprising one or more ligands,may homolytically remove a transferable atom or group from an initiatormolecule and/or a dormant polymer chain (P_(n)—X), to form an activepropagating species, P_(n) ^(●), in an activating reaction with a rateof activation k_(a) which may propagate at a rate k_(p) before aninactive metal-halide catalyst, such as a higher oxidation statetransition metal complex (X-M_(t) ^(n+1)/Ligand) deactivates the activepropagating species, P_(n) ^(●), by donating back a transferable atom orgroup to the active chain end, rate kd_(a) (though not necessarily thesame atom or group from the same transition metal complex). (Scheme 1)

Suitable ligands that may be useful in the reactions and/or formation ofthe (co)polymers, in the various embodiments presented and disclosed inthis application, include those that may be capable of forming a complexwith an active metal-halide catalyst may include, but are not limitedto, tris(2-pyridylmethyl)amine (TPMA); tris[2-(dimethylamino)ethyl]amine(Me6TREN); N,N,N′,N″,N″-pentamethyldiethyletriamine (PMDETA);N,N,N′,N″,N′″,N′″-hexamethyltriethylenetetramine (HMTETA); 4,4′-dinonylbipyridine (dNbipy); or bipyridine (bipy).

Other suitable ligands that may be useful in the reactions and/orformation of the (co)polymers, in the various embodiments presented anddisclosed in this application, may include, but are not limited tocompounds having the formulas:

R³—Z—Z⁴  Formula (II)

R³—Z—(R⁵—Z)_(m)—R⁴  Formula (III)

wherein R³ and R⁴ are independently selected from the group comprisinghydrogen; C₁-C₂₀ alkyl; aryl; heterocyclyl and C₁-C₆ alkyl substitutedwith C₁-C₆ alkoxy; C₁-C₄ dialkylamino; C(═Y) R⁷, C(═Y)R⁸ R⁹, andYC(═Y)R¹⁰,

wherein Y may be NR¹⁰ or O,

wherein R⁷ may be C₁-C₂₀ alkyl, C₁-C₂₀ alkoxy, aryloxy orheterocyclyloxy, and

wherein R⁸ and R⁹ are independently hydrogen or C₁-C₂₀ alkyl, or R⁸ andR⁹ may be joined together to form an C₂-C₅ alkylene group, thus forminga 3- to 5-membered ring, and

wherein R¹⁰ is hydrogen, straight or branched C₁-C₂₀ alkyl or aryl;

wherein Z may be O, S, NR⁶, or PR⁶, wherein R⁶ may be R³ and R⁴, andwherein Z may be PR⁶, wherein R⁶ may be C₁-C₂₀ alkoxy;

wherein each R⁷ may be independently a divalent group selected from thegroup comprising C₃-C₃ cycloalkanediyl, C₃-C₈ cycloalkenediyl,arenediyl, or heterocyclylene, wherein the covalent bonds to each Z maybe at vicinal positions, and C₂-C₄ alkylene and C₂-C₄ alkenylene whereinthe covalent bonds to each Z are at vicinal positions or at β-positions;and

m is from 1 to 6.

For example, compounds of Formulas (II) or (III) may comprise an R³ andR⁴ that may be joined to form a saturated, unsaturated or heterocyclicring. The compounds of Formulas (II) or (III) may comprise compoundswherein each of R³—Z and R⁴, form a ring with the R⁵ group to which theZ may be bound to form a linked or fused heterocyclic ring system. Thecompounds of Formulas (II) or (III) may comprise compounds wherein oneor both of R³ and R⁴ may be heterocyclyl, and in which Z may be acovalent bond; CH₂; a 4- to 7-membered ring fused to R³ or R⁴ or both;CO; porphyrins or porphycenes, which may be substituted with from 1 to 6halogen atoms; C₁-C₆ alkyl groups; C₁-C₆ alkoxy groups; C₁-C₆alkoxycarbonyl; aryl groups; heterocyclyl groups; or C₁-C₆ alkyl groupsfurther substituted with from 1 to 3 halogens.

Other suitable ligands that may be useful in the reactions and/orformation of the (co)polymers, in the various embodiments presented anddisclosed in this application, may include, but are not limited tocompounds comprising the Formula (IV):

R¹¹R¹²C(C(═Y)R⁷)₂  Formula (IV)

wherein Y and R⁷ are as defined above, and wherein each of R¹¹ and R¹²may be independently selected from the group comprising hydrogen;halogen; C₁-C₂₀ alkyl; aryl; or heterocyclyl; and wherein R¹¹ and R¹²may be joined to form a C₃-C₈ cycloalkyl ring or a hydrogenated aromaticor heterocyclic ring, any of which (except for hydrogen and halogen) maybe further substituted with 1 to 5 C₁-C₆ alkyl groups, C₁-C₆ alkoxygroups, halogen atoms, aryl groups, or combinations thereof; and arenesand cyclopentadienyl ligands, wherein the cyclopentadienyl ligand may besubstituted with from 1 to 5 methyl groups, or may be linked through anethylene or propylene chain to a second cyclopentadienyl ligand.

The term “initiator” is understood to mean a molecule comprising one ormore transferable atoms or groups, wherein the initiator is capable ofdecomposing to provide an activated species capable of reacting withunsaturated monomers to form polymeric components. For example, theinitiator may be an alkyl-containing molecule comprising one or moretransferable atoms or groups, such as a halide-substituted alkylinitiator, wherein the halide is the transferable atom or group.

Suitable initiators that may be useful in the reactions and/or formationof the (co)polymers, in the various embodiments presented and disclosedin this application, may include, but are not limited to, alkyl halidesor substituted alkyl halides, such as diethyl 2-bromo-2-methylmalonate(DEBMM); ethyl 2-bromoisobutyrate (EBiB); methyl 2-bromopropionate(MBP); ethyl 2-chloroisobutyrate (ECiB);1,2-bis(2-bromoisobutyryloxy)ethane (2f-BiB); a low molecular weightinitiator comprising one or more transferable atoms or groups, such as asubstituted alkyl halide attached to a low molecular weight molecule, ora substituted alkyl halide attached to a low molecular weight moleculehaving an additional non-initiating functionality; a macroinitiatorhaving one or more transferable atoms or groups, such as a polymericcomponent comprising an alkyl halide moiety, for example, a polystyreneblock having a halide at a terminal end; a solid inorganic material withtethered initiating groups; or a organic material with tetheredinitiating groups.

Other suitable initiators that may be useful in the reactions and/orformation of the (co)polymers, in the various embodiments presented anddisclosed in this application, may include, but are not limited to,having Formula (V):

R¹³R¹⁴R¹⁵C—X  Formula (V)

wherein X comprises Cl, Br, I, OR¹⁶, SR¹, SeR¹, OP(═O)R¹, OP(═O) (OR¹)₂,OP(═O)OR¹, O—N(R¹)₂ and S—(═S)N(R¹)₂,

wherein R¹⁶ is alkyl of from 1 to 20 carbon atoms in which each of thehydrogen atoms may be independently replaced by halide, R¹ is aryl or astraight or branched C₁-C₂₀ alkyl group, and where an N(R¹)₂ group ispresent, the two R¹ groups may be joined to form a 5- or 6-memberedheterocyclic ring; and

wherein R¹³, R¹⁴, and R¹⁵ are each independently selected from the groupcomprising hydrogen, halogen, C₁-C₂₀ alkyl, C₃-C₈ cycloalkyl, X(═Y)R⁷,C(═Y)NR⁸ R⁹, COCl, OH, CN, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl oxiranyl,glycidyl, aryl, heterocyclyl, aralkyl, aralkenyl, C₁-C₆ alkyl in whichfrom 1 to all of the hydrogen atoms are replaced with halogen and C₁-C₆alkyl substituted with from 1 to 3 substituents selected from the groupconsisting of C₁-C₄ alkoxy, aryl, heterocyclyl, C(═Y)R, C(═Y)NR⁸ R⁹,oxiranyl and glycidyl;

wherein R⁷ is alkyl of from 1 to 20 carbon atoms, alkoxy of from 1 to 20carbon atoms, aryloxy or heterocyclyloxy; and R⁸ and R⁹ areindependently hydrogen or alkyl of from 1 to 20 carbon atoms, or R⁸ andR⁹ may be joined together to form an alkylene group of from 2 to 5carbon atoms, thus forming a 3- to 6-membered ring; such that no morethan two of R¹³, R¹⁴ and R¹⁵ are hydrogen.

The term “activated reducing agent” is understood to mean an agentcapable of donating one or more electrons to reduce an inactive metalcatalyst to form an active metal catalyst. For example, the activatedreducing agent may be an activated radical initiator or an activatedfree-radical initiator. The activated reducing agent, such as aradical-containing species, may be formed from decomposition of aradical initiator, for example, thermal decomposition of athermo-activated radical initiator to form a radical-containing speciesor photo-decomposition of a photo-activated radical initiator to form aradical-containing species. The activated reducing agent may initiateand/or perpetuate a polymerization reaction, such as an ATRPpolymerization reaction and/or a ICAR ATRP polymerization reaction, bygenerating or regenerating the active metal catalyst from the inactivemetal catalyst (see Scheme 2).

Some suitable activated reducing agents that may be useful in thereactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may include,but are not limited to, the radical species generated from thedecomposition of azo-containing compounds such as2,2′-azobis(2-methylpropionitrile (AIBN); a peroxide, for example,benzoyl peroxide (BPO), lauroyl peroxide, or cyclohexanone peroxide; aperoxy acid, for example, peroxyacetic acid or peroxybenzoic acid;tert-butyl peracetate; 1,1-bis(tert-butylperoxy)-3,3,5-(dibutylphthalate) trimethylcyclohexane; 2,2′-azobis(4-methoxy-2.4-dimethylvaleronitrile) (V-70); 2,2′-azobis(2.4-dimethyl valeronitrile) (V-65);dimethyl 2,2′-azobis(2-methylpropionate) (V-601);2,2′-azobis(2-methylbutyronitrile) (V-59);1,1′-azobis(cyclohexane-1-carbonitrile) (V-40);2,2′-Azobis[N-(2-propenyl)-2-methylpropionamide] (VF-096); orderivatives or combinations thereof. Other suitable activated reducingagents that may be useful in the reactions and/or formation of the(co)polymers, in the various embodiments presented and disclosed in thisapplication, may include, but are not limited to, the radical speciesgenerated from the decomposition acetophenone; anisoin; anthraquinone;anthraquinone-2-sulfonic acid sodium salt monohydrate; (benzene)tricarbonylchromium; benzyl; benzoin ethyl ether; 4-benzoylbiphenyl;2-benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone;4,4′-bis(diethylamino)benzophenone; camphorquinone;2-chlorothioxanthen-9-one; (cumene)cyclopentadienyliron(II)hexafluorophosphate; dibenzosuberenone; 2,2-diethoxyacetophenone;4,4′-dihydroxybenzophenone; 2,2-dimethoxy-2-phenylacetophenone;4-(dimethylamino)benzophenone; 4,4′-dimethylbenzil;2,5-dimethylbenzophenone; 3,4-dimethylbenzophenone;4′-ethoxyacetophenone; 2-ethylanthraquinone; ferrocene;3′-hydroxyacetophenone; 4′-hydroxyacetophenone; 3-hydroxybenzophenone;4-hydroxybenzophenone; 1-hydroxycyclohexyl phenyl ketone;2-hydroxy-2-methylpropiophenone; 2-methylbenzophenone;3-methylbenzophenone: methybenzoylformate;2-methyl-4′-(methylthio)-2-morpholinopropiophenone; phenanthrenequinone;4′-phenoxyacetophenone; thioxanthen-9-one); or derivatives orcombinations thereof.

Other suitable activated reducing agents that may be useful in thereactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may include,but are not limited to, the radical species comprising a hydroxylradical (HO^(●)); alkoxy radical, such as a substituted alkoxy radical(RO^(●)); peroxy acid radical, such as a substituted peroxy acid radical(R(CO)OO^(●)); nitroso radical (R₂NO^(●)); wherein R may independentlyrepresent an C₁-C₂₀ alkyl group or substituted alkyl group; aryl orsubstituted aryl, or heteroaryl or substituted heteroaryl.

The term “non-activated reducing agent” is understood to mean aprecursor agent that decomposes to form an activated reducing agent. Forexample, a non-activated reducing agent may decompose, such as thermallydecompose or photochemically decompose, or undergo a chemicaltransformation, to form an activated reducing agent. For example, asuitable non-activated reducing agent that may be useful in thereactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may includesthose that decompose to form an activated reducing agent, such as ahydroxyl radical (HO^(●)); alkoxy radical, such as a substituted alkoxyradical (RO^(●)); peroxy acid radical, such as a substituted peroxy acidradical (R(CO)OO^(●)); nitroso radical (R₂NO^(●)); wherein R mayindependently represent an C₁-C₂₀ alkyl group or substituted alkylgroup; aryl or substituted aryl, or heteroaryl or substitutedheteroaryl.

Other suitable non-activated reducing agents that may be useful in thereactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may include,but are not limited to, azo-containing compounds such as2,2′-azobis(2-methylpropionitrile (AIBN); a peroxide, for example,benzoyl peroxide (BPO); lauroyl peroxide, or cyclohexanone peroxide; aperoxy acid, for example, peroxyacetic acid or peroxybenzoic acid;tert-butyl peracetate; 1,1-bis(tert-butylperoxy)-3,3,5-(dibutylphthalate) trimethylcyclohexane; 2,2′-azobis(4-methoxy-2.4-dimethylvaleronitrile) (V-70); 2,2′-azobis(2.4-dimethyl valeronitrile) (V-65);dimethyl 2,2′-azobis(2-methylpropionate) (V-601);2,2′-azobis(2-methylbutyronitrile) (V-59);1,1′-azobis(cyclohexane-1-carbonitrile) (V-40);2,2′-Azobis[N-(2-propenyl)-2-methylpropionamide] (VF-096); orderivatives or combinations thereof. Other suitable activated reducingagents that may be useful in the reactions and/or formation of the(co)polymers, in the various embodiments presented and disclosed in thisapplication, may include, but are not limited to, acetophenone; anisoin;anthraquinone; anthraquinone-2-sulfonic acid sodium salt monohydrate;(benzene) tricarbonylchromium; benzyl; benzoin ethyl ether;4-benzoylbiphenyl;2-benzyl-2-(dimethylamino)-4′-morpholinobutyrophenone;4,4′-bis(diethylamino)benzophenone; camphorquinone;2-chlorothioxanthen-9-one; (cumene)cyclopentadienyliron(II)hexafluorophosphate; dibenzosuberenone; 2,2-diethoxyacetophenone;4,4′-dihydroxybenzophenone; 2,2-dimethoxy-2-phenylacetophenone;4-(dimethylamino)benzophenone; 4,4′-dimethylbenzil;2,5-dimethylbenzophenone; 3,4-dimethylbenzophenone;4′-ethoxyacetophenone; 2-ethylanthraquinone; ferrocene;3′-hydroxyacetophenone; 4′-hydroxyacetophenone; 3-hydroxybenzophenone;4-hydroxybenzophenone; 1-hydroxycyclohexyl phenyl ketone;2-hydroxy-2-methylpropiophenone; 2-methylbenzophenone;3-methylbenzophenone; methybenzoylformate;2-methyl-4′-(methylthio)-2-morpholinopropiophenone; phenanthrenequinone;4′-phenoxyacetophenone; thioxanthen-9-one); or derivatives orcombinations thereof.

The identity of the activated reducing agent or the non-activatedreducing agent, the timing of when the non-activated reducing agent isadded or generates the activated reducing agent, the rate of addition ofthe non-activated reducing agent, and the rate of generating theactivated reducing agent from it's non-activated reducing agentprecursor may effect one or more of the following, including the degreeof polymerization of the unsaturated monomers utilized in thepolymerization reaction, the temperature of the polymerization, theability to control the temperature and/or rate of the polymerization,and the ability to scale a polymerization reaction to an industrialscale sized reaction.

The term “activated-dependent t_(1/2) value” refers to the amount oftime it takes, at a particular activation condition (activationtrigger), for half the concentration of non-activated reducing agent ina system to decompose.

The term “temperature-dependent t_(1/2) value” refers to the amount oftime it takes, at a particular temperature, for half the concentrationof non-activated reducing agent in a system to decompose, such asthermally decompose, to form an activated reducing agent. The term“photo-dependent t_(1/2) value” refers to the amount of time it takes,at a particular electromagnetic exposure (for example light orradiation), for half the concentration of non-activated reducing agentin a system to decompose, such as photo-chemically decompose, to form anactivated reducing agent. The temperature-dependent (or photo-dependent)t_(1/2) values may be similar to or longer than the time for mixing,essentially homogenously (or homogenous), of the non-activated reducingagent in the polymerization reaction system. Suitabletemperature-dependent (or photo-dependent) t_(1/2) values of anon-activated reducing agent to decompose to form an activated reducingagent that may be useful in the reactions and/or formation of the(co)polymers, in the various embodiments presented and disclosed in thisapplication, may include, but are not limited to t_(1/2) values ofbetween 30 sec. and 30 min. at a particular temperature (orelectromagnetic exposure), for example, t_(1/2) values of between 1 min.and 30 min., such as between 1.5 min. and 30 min.; between 2 min. and 30min.; between 3 min. and 30 min.; between 4 min. and 30 min.; between 5min. and 30 min.; between 6 min. and 30 min.; between 7 min. and 30min.; between 8 min. and 30 min.; between 9 min. and 30 min.; between 10min. and 30 min.; between 1 min. and 25 min.; between 1 min. and 20min.; between 1 min. and 15 min.; between 1 min. and 10 min.; between 1min. and 5 min.; between 30 sec. and 20 min.; between 30 sec. and 15min.; between 30 sec. and 10 min.; between 30 sec. and 5 min.; between 5min. and 25 min.; between 5 min. and 20 min.; between 5 min. and 15min.; between 5 min. and 10 min.; or between 10 min. and 20 min. at aparticular temperature (or electromagnetic exposure). Suitabletemperature-dependent (or photo-dependent) t_(1/2) values of anon-activated reducing agent to decompose, at a particular temperature(or electromagnetic exposure), to form an activated reducing agent thatmay be useful in the reactions and/or formation of the (co)polymers, inthe various embodiments presented and disclosed in this application, mayinclude, but are not limited to t_(1/2) values of less than 30 min., forexample, less than 25 min., such as less than 20 min.; less than 15min.; less than 10 min.; less than 9 min.; less than 8 min.; less than 7min.; less than 6 min.; less than 5 min.; less than 4 min.; less than 3min.; less than 2 min.; less than 1 min.; or 30 sec.

As noted above even though ICAR and ARGET ATRP were successfully appliedto the preparation of polymeric materials on the laboratory scale,unexpected problems were encountered when larger scale synthesis wereconducted. These problems are exemplified by the following discussioninvolving scaling-up the ICAR system but are also relevant for ARGETATRP, RAFT and NMP systems.

Precise temperature control throughout the reaction medium isrequired—if this is not achieved, an increase in temperature will causethe radical initiator which is present in the system to decompose at afaster rate and reduce all Cu^(II) to Cu^(I) species. The loss ofCu^(II) deactivator from the system results in an uncontrolledpolymerization in addition to a temperature exotherm. Moreover controlover temperature in an exothermic polymerization reaction is challengingin large scale polymerization procedures due to inefficiencies in heattransfer processes in increasingly viscous media. In standard freeradical polymerization systems viscous polymer solutions can lead to theTrommsdorf effect.

FIG. 1 presents a temperature profile that follows the reactiontemperature during the polymerization of nBA using ARGET ATRP on a 1liter scale. The stirred reaction mixture was heated to 60° C., but dueto the exothermic polymerization process the temperature inside theflask increased above 80° C. The polymerization was not well controlleddue to overheating. This indicates that the use of internal cooling(e.g., a cooling coil) may not be efficient enough to uniformly keep thetemperature within a 2-3° C. temperature range.

Long reaction times due to lower temperatures are used in thepublications discussing ICAR/ARGET, and other CRP systems. Lowertemperatures are targeted to allow a slow generation of radicals (ICAR)or slow reaction of the added reducing agent with the Cu^(II) complexthat had been added at the beginning of the reaction resulting inreaction times that are longer than desired for an economic industrialprocess.

Lower temperatures also increase the viscosity of the system and limitthe range of monomers that can be polymerized to high conversion, forexample monomers that form polymers with a glass transition temperature,Tg, close to or below the reaction temperature reach a glassy state athigh conversion and control is lost

Lack of easy automation of the whole process—as FIG. 1 illustrates,there is no easy way to automate the ICAR/ARGET ATRP with the currentexperimental setup and the presence of an excess of radical initiatorrequires good temperature control.

Although small amounts of catalyst and radical initiator (or reducingagent) are used, a further reduction of the amount of copper catalystand radical initiator is still desired.

Limited accessible molecular weights (MW) of the polymer. For manyapplications, it is essential to prepare high MW polymers; i.e.,polymers with segments above the chain entanglement MW, therefore it isvery important to minimize the effect of “side” reactions between thegrowing radicals and the catalyst that limit the attainable MW. ARGETand ICAR techniques can partially solve this problem due to the use oflow catalyst concentration but the problems noted above with sidereactions associated with transition metal, ligand and reducing agenthave to be resolved by further reducing the concentration of one or moreof the reagents.

The new disclosed method will alleviate/resolve all of the above statedlimitations.

The new method relies on precise continuous control of theCu^(II)/Cu^(I) ratio during an ICAR/ARGET ATRP, or instantaneousconcentration of radicals in RAFT polymerization, or targetedconcentration of the persistent radical present in an NMP process, byfeeding a radical initiator (or reducing agent) to the polymerizationmixture at a controlled rate and optionally using multiple additionports to evenly distribute the agent throughout the whole reactionmedium. Feeding should occur at a such a rate that the amount of radicalinitiator (or reducing agent) added or generated can properly compensatefor all the termination reactions that had occurred since the lastaddition and convert only the appropriate amount of Cu^(II) to Cu^(I)(Scheme 3a). Therefore, the amount of added radical initiator, orreducing agent, at any time of feeding should approximately equal to thenumber of terminated chains (Scheme 3b) formed since the previousaddition.

As disclosed herein if the initiator or reducing agents are slowly addedthroughout the reaction the amount of “excess” activator is controlledand any increase in the rate of decomposition or reduction is avoided.If the reaction temperature should rise stopping addition eventuallystops the reaction. Suitable reducing agents are disclosed inincorporated references.

In contrast to the present ARGET and ICAR procedures the amount ofinitiator added in a single addition may be less than the stoichiometricamount required to reduce all of Cu^(II) present in the reactor toCu^(I). This will be accomplished by the presence, or activation, of avery small amount of residual initiator (or reducing agent) in thereactor at any time. The amount of initiator fed to the reactor, orgenerated, may match the amount of termination that occurs since theprevious addition/activation. If temperature would locally increase, dueto a poor heat exchange or local overheating, the excess reduction ofCu^(II) to Cu^(I) is thereby easily contained and limited to only theamount of initiator locally present in the reaction medium. Thus,instead of adding the entire amount initiator/reducing agent at thebeginning of the reaction and counting on fortuitous control over therate of decomposition of the initiator to maintain control, only as muchreducing agent/initiator as needed will be fed to the system, orinstantaneously generated, during the entire process while limiting theeffect of temperature fluctuations on the rate of reduction of Cu^(II)to Cu^(I).

If such conditions are fulfilled, ‘starving conditions’ for reducingagent or radical initiator during polymerization process will beachieved and will result in the desired-constant Cu^(II) to Cu^(I)ratio. A sufficiently high amount of Cu^(II) is a requirement forproduction of (co)polymers with narrow molecular weight distribution ina controlled ATRP process, equation 1:

$\begin{matrix}{\frac{M_{w}}{M_{n}} = {1 + \frac{1}{{DP}_{n}} + {\left( \frac{\left\lbrack {R - X} \right\rbrack_{o}k_{p}}{k_{da}\left\lbrack {X - {Cu}^{II}} \right\rbrack} \right)\left( {\frac{2}{p} - 1} \right)}}} & (1)\end{matrix}$

In one embodiment of the process after the desired ratio ofCu^(II)/Cu^(I) is attained only a very small amount of radical initiator(or reducing agent) will be instantaneously present in any volumefraction of the polymerization system. As a result, the ratio ofCu^(II)/Cu^(I) will be kept within the appropriate range to producepolymers with narrow molecular weight distribution, equation 1.

Several advantages accrue from the new ‘feeding’ method as a result ofkeeping the instantaneous concentration of radical initiator (or otherreducing agent) very low in the polymerization system.

No need of precise temperature control—the only requirement will be tokeep the temperature high enough to quickly decompose the added radicalinitiator, while still allowing sufficient time for distribution of theinitiator throughout the targeted volume of the reaction mixture afteraddition. Multiple addition ports can be used for larger scaleindustrial equipment to minimize the time required for diffusion of theactivator to all parts of the reaction medium or only sufficient lightto decompose the required amount of photo-responsive initiators ispulsed into the reactor.

Safe process for exothermic reactions—the effect of an exothermicreaction will be diminished by very low instantaneous concentration ofradical initiator (or reducing agent) since the added tiny amount ofinitiator/reducing reagent cannot overwhelm the excess Cu^(II) presentin the reactor. This means that in the absence of addedinitiator/activator only a controlled ATRP reaction can occur and thisreaction will slow down if an increased concentration of Cu^(II) isgenerated by termination reactions since excess Cu^(II) acts to increasethe rate of deactivation of any growing radical chains.

Shorter reaction times—due to the use of higher reaction temperatures,reactions can be much faster since the rate constant of propagationincreases with temperature much more than that of termination therebyretaining a high mole fraction of “living” chains. Higher reactiontemperature also results in lower viscosity systems at any particularconversion and hence the reaction can be driven to higher conversion aswell as preparation of higher molecular weight polymers. The conversionof monomer to polymer can therefore exceed 80%, preferably exceed 90%and optimally exceed 95%.

Full automation possible—as only tiny amounts of radical initiator (orreducing agent) are present at any instant in the polymerization medium,the reaction should stop as soon as feeding/activation is stopped. Thus,the rate of polymerization is controlled by the rate of generation ofradicals by decomposition of the radical initiator (or by theconcentration of reducing agent) and is stopped in any emergencyconditions simply by incorporating a feedback loop that stops additionof radical initiator, reducing agent or activation of an addedphoto-responsive initiator.

Continuous feeding of initiator/reducing agent in order to minimizesteady state residual concentration of the radical initiator therebyreducing initiator based side reactions.

Lower amounts of transition metal and ligand are required in thereaction. An excess of ligand is normally used in ARGET and ICARpolymerizations to counteract possibility of formation of amonomer/transition metal complex.

Possible control over PDI by increasing the Cu^(I)/Cu^(II) ratio andk_(p), which depends on monomer type and temperature.

One pot synthesis of block copolymers since higher chain endfunctionality is retained.

The molar % conversion that may be achieved by the polymerizationreaction processes disclosed herein, may include, but is not limited to,between 65-100 molar % conversion, relative to the initial molar amountof unsaturated monomer introduced into the polymerization system,wherein the molar % conversion refers to the molar amount of unsaturatedmonomer converted into the form of a polymer or polymeric component. Forexample, the molar % conversion may be at least 65 molar % conversion,such as up to 100 molar % conversion, example, up to 99 molar %conversion, or up to 98 molar % conversion; and/or at least 70 molar %;at least 75 molar %; at least 80 molar %; at least 85 molar %; at least90 molar %; at least 95 molar %; at least 97 molar %; or at least 98molar % conversion, relative to the initial molar amount of unsaturatedmonomer introduced into the polymerization system.

Suitable temperatures to begin and/or conduct the polymerizationreaction that may be useful in the reactions and/or formation of the(co)polymers, in the various embodiments presented and disclosed in thisapplication, may include, but are not limited to, between 25° C. and thetemperature at which the t_(1/2) conversion rate is at least 30 sec.(i.e., temperature at t_(1/2)=30 sec.), for example, between 25° C. andtemperature at t_(1/2)=1 min., such as between 25° C. and temperature att_(1/2)=2 min.; between 25° C. and temperature at t_(1/2)=3 min.;between 25° C. and temperature at t_(1/2)=4 min.; between 25° C. andtemperature at t_(1/2)=5 min.; between 25° C. and temperature att_(1/2)=6 min.; between 25° C. and temperature at t_(1/2)=7 min.;between 25° C. and temperature at t_(1/2)=8 min.; between 25° C. andtemperature at t_(1/2)=9 min.; between 25° C. and temperature att_(1/2)=10 min.; between 25° C. and temperature at t_(1/2)=15 min.;between 25° C. and temperature at t_(1/2)=20 min.; between 25° C. andtemperature at t_(1/2)=25 min.; or between 25° C. and temperature att_(1/2)=30 min.

Suitable molar ratios of unsaturated monomers to initiator that may beuseful in the reactions and/or formation of the (co)polymers, in thevarious embodiments presented and disclosed in this application, mayinclude, but are not limited to molar ratios of between 25-5,000:1, forexample, between 100-5,000:1, such as between 250-5,000:1; between500-5,000:1; between 750-5,000:1; between 1,000-5,000:1; between1,500-5,000:1; between 2,000-5,000:1; between 2,500-5,000:1; between3,000-5,000:1; between 3,500-5,000:1; between 4,000-5,000:1; or molarratios of between 4,500-5,000:1.

Suitable ratios of inactive metal catalyst to initiator in thepolymerization mixture that may be useful in the reactions and/orformation of the (co)polymers, in the various embodiments presented anddisclosed in this application, may include, but is not limited to0.001-0.5:1, for example, between 0.003-0.5:1, such as between0.005-0.5:1; between 0.007-0.5:1; between 0.010-0.5:1; between0.015-0.5:1; between 0.020-0.5:1; between 0.025-0.5:1; between0.04-0.5:1; between 0.05-0.5:1; between 0.07-0.5:1; between 0.1-0.5:1;between 0.15-0.5:1; between 0.2-0.5:1; between 0.25-0.5:1; between0.3-0.5:1; between 0.35-0.5:1; between 0.4-0.5:1; or molar ratios ofbetween 0.45-0.5:1 and/or the metal catalyst may be present in themixture in an amount of less than 250 ppm by mass relative to the totalmass of the polymerization mixture.

Suitable amounts of metal catalyst that may be useful in the reactionsand/or formation of the (co)polymers, in the various embodimentspresented and disclosed in this application, may include amounts in therange of 0.1 parts per million (ppm) by mass to 250 ppm by mass relativeto the total mass of the polymerization mixture, for example, between0.1 and 225 ppm, such as between 0.1 and 200 ppm; between 0.1 and 175ppm; between 0.1 and 150 ppm; between 0.1 and 125 ppm; between 0.1 and100 ppm; between 0.1 and 75 ppm; between 0.1 and 50 ppm; between 0.1 and25 ppm; between 0.1 and 20 ppm; between 0.1 and 15 ppm; between 0.1 and10 ppm; between 0.1 and 5 ppm; between 0.1 and 3 ppm; or amounts ofbetween 0.1 and 1 ppm.

Suitable ratios of the amount of non-activated reducing agent toinitiator that may be useful in the reactions and/or formation of the(co)polymers, in the various embodiments presented and disclosed in thisapplication, may include, but is not limited to 0.01-0.5:1, for example,between 0.02-0.5:1, such as between 0.03-0.5:1; between 0.04-0.5:1;between 0.05-0.5:1; between 0.06-0.5:1; between 0.07-0.5:1; between0.08-0.5:1; between 0.09-0.5:1; between 0.1-0.5:1; between 0.2-0.5:1;between 0.3-0.5:1; between 0.4-0.5:1; or molar ratios of between0.45-0.5:1.

Suitable polymers formed by methods disclosed herein that may be usefulin the reactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may have amolecular weight of greater than 100,000 g/mol, for example, between100,000 g/mol and 2,000,000 g/mol, such as between 125,000 g/mol and1,750,000 g/mol; between 150,000 g/mol and 1,750,000 g/mol; between200,000 g/mol and 1,500,000 g/mol; between 225,000 g/mol and 1,250,000g/mol; between 125,000 g/mol and 1,000,000 g/mol; between 125,000 g/moland 900,000 g/mol; between 125,000 g/mol and 800,000 g/mol; between125,000 g/mol and 700,000 g/mol; between 150,000 g/mol and 650,000g/mol; between 200,000 g/mol and 600,000 g/mol; between 225,000 g/moland 650,000 g/mol; between 250,000 g/mol and 550,000 g/mol; between350,000 g/mol and 500,000 g/mol; between 300,000 g/mol and 500,000g/mol; between 350,000 g/mol and 750,000 g/mol; between 100,000 g/moland 1,750,000 g/mol; between 100,000 g/mol and 1,500,000 g/mol; between100,000 g/mol and 1,125,000 g/mol; between 100,000 g/mol and 1,000,000g/mol; between 100,000 g/mol and 750,000 g/mol; between 100,000 g/moland 500,000 g/mol; between 100,000 g/mol and 400,000 g/mol; between100,000 g/mol and 300,000 g/mol; or between 100,000 g/mol and 200,000g/mol.

Suitable polymers formed by methods disclosed herein that may be usefulin the reactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may havedegrees of polymerization within a polymeric arm of between 10 and5,000, such as between 10 and 4,500; between 10 and 4,000; between 10and 3,500; between 10 and 3,000; between 10 and 2,500; between 10 and2,000; between 10 and 1,500; between 10 and 1,000; between 10 and 900;between 10 and 800; between 10 and 700; between 10 and 600; between 10and 500; between 10 and 400; between 10 and 300; between 10 and 200;between 10 and 100; between 10 and 75; between 10 and 50; or between 10and 25.

Suitable copolymers formed by methods disclosed herein that may beuseful in the reactions and/or formation of the (co)polymers, in thevarious embodiments presented and disclosed in this application, maycomprises copolymeric segments having degrees of polymerization ofbetween 10 and 5,000, such as between 10 and 4,500; between 10 and4,000; between 10 and 3,500; between 10 and 3,000; between 10 and 2,500;between 10 and 2,000; between 10 and 1,500; between 10 and 1,000;between 10 and 900; between 10 and 800; between 10 and 700; between 10and 600; between 10 and 500; between 10 and 400; between 10 and 300;between 10 and 200; between 10 and 100; between 10 and 75; between 10and 50; or between 10 and 25.

For example, a suitable copolymer formed by methods disclosed hereinthat may be useful in the reactions and/or formation of the(co)polymers, in the various embodiments presented and disclosed in thisapplication, may comprises copolymeric segments of styrene residues andacrylic acid residues, wherein the degree of polymerization of thestyrene residues may be between 10 and 5,000, such as between 10 and4,500; between 10 and 4,000; between 10 and 3,500; between 10 and 3,000;between 10 and 2,500; between 10 and 2,000; between 10 and 1,500;between 10 and 1,000; between 10 and 900; between 10 and 800; between 10and 700; between 10 and 600; between 10 and 500; between 10 and 400;between 10 and 300; between 10 and 200; between 10 and 100; between 10and 75; between 10 and 50; or between 10 and 25; and wherein the degreeof polymerization of the acrylic acid residues may be between 10 and5,000, such as between 10 and 4,500; between 10 and 4,000; between 10and 3,500; between 10 and 3,000; between 10 and 2,500; between 10 and2,000; between 10 and 1,500; between 10 and 1,000; between 10 and 900;between 10 and 800; between 10 and 700; between 10 and 600; between 10and 500; between 10 and 400; between 10 and 300; between 10 and 200;between 10 and 100; between 10 and 75; between 10 and 50; or between 10and 25.

Preparing a polymer comprising a degree of polymerization of, forexample comprising styrene residues, of between 15 and 5,000, forexample, according to the process described herein, may take between 4to 60 hours, wherein the polymerization reaction temperature isconducted at a temperature wherein the temperature-dependent (orphoto-dependent) t_(1/2) values of a non-activated reducing agent todecompose to form an activated reducing agent may be between 30 sec. and30 min. Similarly, preparing a polymer comprising a degree ofpolymerization of, for example comprising styrene residues, of between60 and 500, for example, according to the process described herein, maytake between 10 to 12 hours, wherein the polymerization reactiontemperature is conducted at a temperature wherein thetemperature-dependent (or photo-dependent) t/2 values of a non-activatedreducing agent to decompose to form an activated reducing agent may bebetween 30 sec. and 30 min. The temperature for the process may comprisea temperature of 10° C. below the boiling point of the unsaturatedmonomer, such as 15° C., 20° C., 25° C. below the boiling point of theunsaturated monomer. The temperature of the process may comprise atemperature wherein the polymerization rate may be accelerated by atleast 10%, for example, 15%, 20%, 30%, 50%, 75%, or 100%.

Preparing a polymer comprising a degree of polymerization of, forexample comprising acrylate residues, of between 15 and 5,000, forexample, according to the process described herein, may take between 2to 20 hours, wherein the polymerization reaction temperature isconducted at a temperature wherein the temperature-dependent (orphoto-dependent) t_(1/2) values of a non-activated reducing agent todecompose to form an activated reducing agent may be between 30 sec. and30 min. Similarly, preparing a polymer comprising a degree ofpolymerization of, for example comprising acrylate residues, of between60 and 500, for example, according to the process described herein, maytake between 3 to 5 hours, wherein the polymerization reactiontemperature is conducted at a temperature wherein thetemperature-dependent (or photo-dependent) t_(1/2) values of anon-activated reducing agent to decompose to form an activated reducingagent may be between 30 sec. and 30 min. The temperature for the processmay comprise a temperature of 10° C. below the boiling point of theunsaturated monomer, such as 15° C., 20° C., 25° C. below the boilingpoint of the unsaturated monomer. The temperature of the process maycomprise a temperature wherein the polymerization rate may beaccelerated by at least 10%, for example, 15%, 20%, 30%, 50%, 75%, or100%.

Suitable methods for preparing a polymer from unsaturated monomers thatmay be useful in the reactions and/or formation of the (co)polymers, inthe various embodiments presented and disclosed in this application, maycomprise forming a polymer having a degree of polymerization of 200 orless over a polymerization reaction time of 12 hours or less. Forexample, the prepared polymer may have a degree of polymerization ofbetween 10 and 200, such as between 10 and 175; between 10 and 150;between 10 and 125; between 10 and 100; between 10 and 75; between 10and 50; between 25 and 200; between 50 and 200; between 75 and 200;between 100 and 200; between 125 and 200; between 150 and 200; between175 and 200; or combinations thereof, that may be prepared over apolymerization reaction time of between 2 hours and 12 hours, such asbetween 3 and 10 hours; between 4 and 9 hours; between 5 and 8 hours;between 6 and 10 hours; between 6 and 8 hours; between 2 and 7 hours;between 3 and 10 hours; or combinations thereof.

Suitable polymers formed by methods disclosed herein that may be usefulin the reactions and/or formation of the (co)polymers, in the variousembodiments presented and disclosed in this application, may have apolydispersity index (PDI) of less than 2.5, for example, a PDI of lessthat 2.0, such as less than 1.7. For example, a polymer formed bymethods disclosed herein may have a PDI of between 1.0 to 2.5, such asbetween 1.0 and 2.3; between 1.0 and 2.0; between 1.0 and 1.9; between1.0 and 1.8; between 1.0 and 1.7; between 1.0 and 1.6; between 1.0 and1.5; between 1.0 and 1.4; between 1.0 and 1.3; between 1.0 and 1.2;between 1.0 and 1.1; between 1.05 and 1.75; between 1.1 and 1.7; between1.15 and 1.65; or between 1.15 and 1.55.

In operation, the addition of the non-activated reducing agent incertain embodiments, beyond the initial amount provided to thepolymerization system, may be influenced by a number of factors, such asthe desire to allow for the dispersion or substantial dispersion of thenon-reducing agent into the polymerization system prior to it generatingthe activated reducing agent. For instance, one needs to consider thetemperature of the polymerization reaction at which a non-activatedreducing agent, such as a thermo-activated reducing agent, like AIBN, isadded, as this is related to the rate of conversion, such as t_(1/2)rate of thermal decomposition, to form the activated reducing agent.

For example, in an effort to provide even- or substantiallyeven-dispersal of the non-activated reducing agent prior to itsconversion to an activated reducing agent, such factors as the rate ofaddition of the non-activated reducing agent, or the amount of thenon-activated reducing agent that is added, or both, need to beconsidered and may be influenced by this relationship between reactiontemperature and the rate of conversion to form the activated reducingagent. For example, if the conversion rate of the non-activated reducingagent at the particular reaction temperature is shorter than the time ittakes to disperse the agent into the system evenly (or substantiallyevenly), then there is the potential for localized exotherms or“hot-spots” to occur, which can be both a safety hazard, but also impactthe molecular weights and PDI of the polymer products formed due to highor very high concentrations of radicals in these localized regions. Ifthe conversion rate of the non-activated reducing agent at theparticular reaction temperature is much longer than the time it takes todisperse the agent into the system evenly (or substantially evenly),then this may decrease the efficiency of the polymerization reactionprocess, unnecessarily extending the overall time of the reaction. Itmay also result in the accumulation of higher amounts of reducing agentin the polymerization mixture which may be a safety hazard. In view ofthese concerns, the rate of addition of the non-activated reducing agentmay be continuous, non-continuous, periodic or intermittent, adjustable,or combinations thereof, to achieve an even dispersal or substantiallyeven dispersal of the non-activated reducing agent before it generatesan activated reducing agent that subsequently activates an inactivemetal-halide catalyst to drive the polymerization reaction.

In certain embodiments, the particular relationship between the reactiontemperature and the rate of conversion, such as t_(1/2) rate of thermaldecomposition, to form an activated reducing agent from a non-activatedreducing agent, may provide an ability to start or stop (“start-stop”)the polymerization reaction in a safe, effective, and convenient manner.For instance, the progress, degree and/or rate of the polymerizationreaction may be regulated or controlled by the rate of addition and/orthe amount of the non-activated reducing agent that is added. Forexample, the progress, degree and/or rate of the polymerization reactionmay be stopped by stopping the addition of the non-activated reducingagent may allow for the reaction to stop in a relatively short period oftime (such as between 3-30 min.). Similarly, the progress, degree and/orrate of the polymerization reaction may be started by starting theaddition of the non-activated reducing agent may allow for the reactionto start in a relatively short period of time (such as between 3-30min., for example, within the t_(1/2) conversion rate at the reactiontemperature). In certain embodiments, the polymerization reaction mayundergo a series of start-stop cycles during the production of aparticular polymer product. Reasons for wanting to have this ability tostart-stop the polymerization reaction, especially on industrial scale,may include, but are not limited to, safety concerns; determiningproduct quality, such as regulating the molecular weights of theproducts or the degree of polymerization; convenience concerns, such aschange of personnel shifts; altering reagent feeds, such as altering themonomer feed, for example, changing monomer identity to produce acopolymer or to add a cross-linker to form a star-macromolecule polymer;and/or combinations thereof.

For example, the determination of when to conduct a start-stop processregarding the addition of the non-activated reducing agent may be basedon the molar % conversion that has been achieved by a polymerizationreaction process, converting an unsaturated monomer converted into theform of a polymer or polymeric component. The molar % conversion thatmay signal to start, stop, or adjust the rate of an addition of aportion, or further portion, of a non-activated reducing agent mayinclude, but is not limited to, at least 10 molar % conversion, relativeto initial molar amount of unsaturated monomer introduced into thepolymerization system, for example, 40 molar % conversion, such as atleast 20 molar %; at least 25 molar %; at least 30 molar %; or at least35 molar % conversion, relative to initial molar amount of unsaturatedmonomer introduced into the polymerization system.

In certain embodiments, the polymers prepared according to the processesdescribed herein may be utilized in the formation of polymercompositions comprising star macromolecules. For example, the preparedstar macromolecule may have a core and five or more polymeric arms. Thenumber of arms within a prepared star macromolecule may vary across thecomposition of star molecules. The arms on a prepared star macromoleculemay be covalently attached to the core of the star. The arms of aprepared star macromolecule may comprise one or more polymer segments orco-polymeric segments (such as block co-polymers), and at least one armand/or at least one segment may exhibit a different solubility from atleast one other arm or one other segment, respectively, in a referenceliquid of interest. The prepared star macromolecule may be a mikto starmacromolecule.

In certain embodiments, the polymers prepared according to the processesdescribed herein may be utilized to prepare a star macromolecule,comprising: a plurality of arms comprising at least two types of arms,wherein the degree of polymerization of a first-arm-type is greater thanthe degree of polymerization of a second-arm-type, and wherein saidfirst-arm-type has a distal end portion that is hydrophobic. The starmacromolecule may be formed by first forming or obtaining thehydrophobic portion and then forming the remaining portion of thefirst-arm-type from the end of the hydrophobic portion and thesecond-arm-type in a one-pot synthesis wherein the poylmerization of thesecond portion of the first-arm-type is commenced prior to theinitialization of the second-arm-type but there is at least some pointwherein portions, e.g., substantial portions, of the first-arm-type andsecond-arm-type are being polymerically extended simultaneously.

In certain embodiments, the polymers prepared according to the processesdescribed herein may be utilized to prepare a star macromoleculecomposition, wherein the number of arms on any particular starmacromolecule may vary across the population of star macromolecules ineach composition, due to the synthetic process used for the synthesis ofthe composition. This process is called “arm first” method.

Suitable star macromolecules that may be formed at least in part by thereactions and/or (co)polymers, in the various embodiments presented anddisclosed in this application, may include those having a wide range oftotal number of arms, for example, a star macromolecule may comprisegreater than 15 arms. For example, a suitable star macromolecule maycomprise between 15 and 100 arms, such as between 15 and 90 arms;between 15 and 80 arms; between 15 and 70 arms; between 15 and 60 arms;between 15 and 50 arms; between 20 and 50 arms; between 25 and 45 arms;between 25 and 35 arms; between 30 and 45 arms; or between 30 and 50arms.

ABBREVIATIONS USED IN THE FOLLOWING EXAMPLES

ATRP atom transfer radical polymerization

ARGET activator regenerated by electron transfer

ICAR initiator for continuous activator regeneration

DEBMM diethyl 2-bromo-2-methylmalonate

BrPN 2-bromopropionitrile

TPMA tris(2-pyridylmethyl)amine

AIBN 2,2′-azobis(2-methylpropionitrile

V-70 2,2′-azobis(4-methoxy-2.4-dimethyl valeronitrile)

EXAMPLES AND DISCUSSION OF EXAMPLES

During the initial attempts to scale up ARGET/ICAR ATRP detailed belowit became clear that the number of variables that have to be controlledare significantly greater than initially expected as the scale of thereactions was increased. Therefore in order to define optimalpolymerization conditions for the new ‘feeding’ methods for ICAR ATRP,it was crucial to generate a set of parameters for the feeding rate ofradical initiator that takes into account the specific type of monomer,reaction temperature, type of radical initiator, concentrations andratios of all reagents, etc. Kinetic modeling was conducted to selectinitial conditions to reach synthetic targets and understand factorsaffecting control under many different conditions. In addition, someadditional parameters such as rate of diffusion of the initiator fed tothe solution, heat transfer related to the reactor design, viscosity ofpolymer solution at know conversion and others were taken into account.

The potential starting points generated by computer modeling of thecritical process factors were investigated by performing experiments on1 L scale with a single source of added reducing agent. All of thesefactors were carefully studied to achieve good control over thepolymerization process and to provide the kinetic data required forfurther scale up to industrial scale equipment.

Computer Simulations

The synthetic conditions of the new ‘feeding’ method for ICAR ATRP weremodeled via computer. Comprable software has been successfully appliedto many polymerization systems including normal and ICAR ATRP[Macromolecules 2007, 40, 6464-6472.] and allows precise calculation ofthe concentration of all species (including intermediates) in a reactionversus time or conversion. It also permits one to estimate the molecularweight distributions of all polymeric species. All required parameterssuch as rate constants, initial concentrations of all reactant and therate of feeding of radical initiator are entered in the workshopassistant of the software. Computer simulations are simple to performand can be completed in a short period of time, thus a broad range ofdifferent variables can be studied to optimize the new ‘feeding’ methodfor an exemplary ICAR ATRP. Typical variations for specific monomers arediscussed below. In ICAR it is crucial to correlate feeding/generationrate of the radical initiator (RI) with other parameters (temperature,type of radical initiator, etc.) in order to obtain good control overthe polymerization process.

Computer Simulations for Polymerization of Methyl Methacrylate

FIG. 2 shows the initial set of parameters used for computer simulationsconducted for polymerization of MMA with continuous feeding of twodifferent radical initiators at a series of temperatures targetingdifferent DP. Preliminary results from initial simulation of theproposed method suggested that this approach to process conditionevaluation is possible.

The general ratio of reagents for one exemplary non-limiting example ofthe new ‘feeding’ method for ICAR ATRP with 50 ppm amount of Cu was:M/R—X/CuBr₂/ligand/RI=X/1/0.01/0.01/0.05 in bulk at temperature T (whereM—monomer, R—X—alkyl halide initiator, RI—radical initiator, X=100,500). Commercially available tris(2-pyridylmethyl)amine (TPMA) was usedas the initial exemplary ligand and diethyl 2-bromo-2-methylmalonate(DEBMM) was used as an exemplary alkyl halide initiator in thepolymerization systems. Other catalysts and initiators were alsoevaluated. The RI was fed to the reaction medium at two different ratesand the targeted reaction time was set for either 6 or 24 hours.

Therefore the initial set of simulations for polymerization of MMA usingthe new ‘feeding’ method were conducted with 50 ppm amount of Cu and theratio of reagents: MMA/DEBMM/Cu^(II)Br₂/TPMA/RI=X/1/0.01/0.01/0.05 inbulk. Two different radical initiators were used,2,2′-azobis(2-methylpropionitrile) (AIBN), with a 10 hour half-lifedecomposition temperature at 65° C.) and2,2′-Azobis(4-methoxy-2.4-dimethyl valeronitrile) (V-70), with a 10 hourhalf-life decomposition temperature at 30° C.). Different temperatureswere applied for polymerizations with AIBN (70, 80, 90° C.) and V-70(45, 55, 70° C.) as radical initiators. They provide half-lifedecomposition times of 300, 70, 20 minutes, and 60, 15, 3 minutes,correspondingly. Two different degrees of polymerizations will be chosen(DP=X=100, 1000) in order to cover a typical range of molecular weightsaccessible with the new method. The feeding rate of the radicalinitiator will be set for 6 and 24 h as a final time.

The overall volume of the solution of radical initiator that was fed tothe reaction was less than 10% versus volume of monomer (reactionvolume), i.e., while dilute solutions of the initiator were added thetotal added solvent will be within limits associated with “monomer”removal from a bulk polymerization. The final objective was to provideconditions for polymerization of a range of methacrylate monomers.

It is expected that a broad range of type I and type II photoinitiatorscan be employed and simulations will examine the effects of therate/intensity of stimulation.

Other simulations designed to provide starting conditions forpolymerization reactions examined periodic addition/formation of radicalinitiators or reducing agents for transition metal complexes studied arange of parameters including:

type of monomer (different rate constants of propagation and terminationas well as activation and deactivation will be applied to differenttypes of monomers and catalysts). Styrene, n-butyl acrylate and methylmethacrylate were the initial three exemplary monomers as they cover thethree largest classes of radically polymerizable monomers.

Type of radical initiator (different rate constants of decompositions,also depending on temperature).

Type of catalyst (different rate constants of activation anddeactivation).

Degree of polymerization (DP) (both low and high MW).

Temperature (change of decomposition rates of radical initiator and allother rate constants).

Rate and method of feeding for the radical initiator/activator (slow,fast and periodical).

Other parameters such as ratios and concentrations of reagents wereinitially kept constant but later were also varied in order to minimizethe amount of copper and initiator and optimize polymerization rate.

FIG. 3 shows the simulated kinetic plot, molecular weight andpolydispersity (PDI) vs. conversion and GPC trace of PMMA prepared viathe feeding method for ICAR ATRP. The results shown in FIG. 3 are forsimulations done for experimental conditions:MMA/DEBMM/Cu^(II)Br₂/TPMA/AIBN=500/1/0.025/0.025/0.05 in bulk at 90° C.,with a constant concentration of initiator added over a feeding time 10h. The linear kinetics, good control over molecular weight, low PDI andmonomodal distribution of molecular weight show that the polymerizationcould be well controlled.

A series of simulations were conducted using methyl methacrylate, butylacrylate and styrene as exemplary monomers. The results from the initialseries of simulations for these three monomers provided starting pointsfor reactions conducted in a 1 L reactor. Based on the experimentalresults, some additional changes can be made in the simulation to fullyoptimize the investigated polymerization system.

A similar series of simulations will be conducted using aphotoresponsive initiator to determine if the rate of radical formationcan be controlled by controlled photo-stimulation.

A similar series of simulations will be conducted using a reducing agentto determine if ARGET ATRP con be conducted under “starved” feedingconditions and result in improved control.

Polymerization Experiments

Polymerization experiments using the new ‘feeding’ method for ICAR ATRPwere carried out for three representative monomers (MMA, nBA and St) ata 1 liter scale in a Ace Glass reactor equipped with a heating mantle,mechanical stirrer and thermocouple. At this scale of the reaction,challenges related with heat transfer and viscosity, as well asexothermicity, become important; as discussed the background section andshown in FIG. 1. These factors are not taken into account by computermodeling software. Thus, some adjustments were made in order to fullyoptimize the new ‘feeding’ method in the actual ICAR ATRP experimentalexamples.

Nonetheless, initially each monomer was polymerized with the conditionsinitially optimized via computer simulations. Additional adjustmentswere made in order to further increase control over the polymerization.These adjustments are specified for each monomer below.

The run numbers listed below were employed for internal tracking of theexperiments and do not have any further significance.

Comparative Example C1

ARGET ATRP of MMA with Sn(EH)2 as reducing agent: Run 07-004-83. Scale:in 1 L reactor.

Conditions: MMA/DEBMM/CuBr₂/TPMA/Sn(EH)₂=2200/1/0.015/0.06/0.1 in DMF(0.05 volume eq. vs. MMA), (7 ppm of Cu), T=65° C.

The polymerization was performed in bulk and at 65° C. The reaction waswell controlled with Mn close to theoretical values and low PDI. Thekinetics of the reaction and GPC results of the polymer samples takenduring the experiment are shown in FIG. 4. After 27.6 hours the finaldegree of polymerization (DP) of the polymer was 890 and theM_(n(GPC))=90,000 with a polydispersity of 1.17. A small tailing to thelow molecular weight is visible on GPC traces.

Comparative Example C2

Chain extension of polymer prepared in example C1: Run 07-004-84. Scale:25 mL Schlenk flask.

Conditions: St/PMMA/CuBr₂/TPMA/Sn(EH)₂=5000/1/0.02/0.06/0.2 in anisole(0.1 volume eq. vs. St), (4 ppm of Cu) T=80° C. (07-004-83 asmacroinitiator)

The kinetics of the reaction and GPC results of the experiment are shownin FIG. 5.

The GPC results of the polymer samples taken during the experimentindicates that the chain extension of the PMMA macroinitiator formed inexample C1 with St was not fully successful. One can conclude thatdespite the narrow PDI of the macroinitiator the chain-end functionalityis not very high, after 4000 minutes reaction some of macroinitiator wasstill not chain extended resulting in bimodal molecular weightdistribution.

One reason for low chain-end functionality is a transfer reaction of thegrowing radical to Sn(EH)₂ indicating that a different reducing agenthas to be used in order to synthesize PMMA with high molecular weightand high chain-end functionality.

Comparative Example C3

ICAR ATRP of MMA with AIBN as radical initiator. Run: 07-004-85. Scale:1 L reactor

Conditions: MMA/DEBMM/CuBr₂/TPMA/AIBN=2400/1/0.02/0.025/0.15 in anisole(0.03 volume eq. vs. MMA), (8 ppm of Cu), T=55° C.

The kinetics of the reaction and GPC results of the polymer samplestaken during the experiment are shown in FIG. 6. In this comparatorexample polymerization of MMA was performed in bulk at 55° C. in thepresence of AIBN instead of Sn(EH)₂ to avoid transfer reactions toSn(EH)₂ apparent during the chain extension reaction described inexample C2. After 45.5 hours reaction the DP of the polymer was 894 andthe MW 89,500 with M_(n) close to theoretical values and low PDIindicating the polymerization was well controlled. No tailing is visibleon GPC traces suggesting that no transfer reactions occurred during thepolymerization process.

Comparative Example C4

Chain extension of polymer prepared in example C3. Run: 07-004-89.Scale: 25 mL Schlenk flask.

Conditions: St/PMMA/CuBr₂/TPMA/Sn(EH)₂=5000/1/0.02/0.06/0.2 in anisole(0.1 volume eq. vs. St), (4 ppm of Cu), T=80° C., time=40.2 hr. SampleC3, 07-004-85 as macroinitiator

The kinetics of the reaction and GPC results of the polymer samplesduring experiment are shown in FIG. 7. The chain extension of PMMA C3with St was successful. Chain-end functionality of PMMA C3 is muchhigher than in PMMA C1, no bimodal distribution of molecular weight wasobserved after extension, only small tailing visible on GPC traces ofthe polymer samples taken during the experiment. This result proves thatone reason of low chain-end functionality of PMMA C1 is the transferreaction to Sn(EH)₂. Indicating that either ICAR ATRP or anon-transition metal based reducing agent has to be used in order toobtain PMMA with higher chain-end functionality

Comparative Example C5

ICAR ATRP of MMA with AIBN as radical initiator. Run: 08-006-48. Scale:in 1 L reactor.

Conditions: MMA/DEBMM/CuBr₂/TPMA/AIBN=2400/1/0.025/0.03/0.2 in bulk(anisole as internal standard), (10 ppm of Cu), T=55° C., time=41.6hours.

The kinetics of the reaction and GPC curves of the polymer samples takenduring the experiment are shown in FIG. 8 indicating that the finalpolymer had a DP of 1414 and M_(n(GPC)) 141,600. The polymerization waswell controlled at the beginning. The final PDI, sample 3 was slightlyhigher than sample 2, but significant temperature fluctuations wereencountered when higher conversion was attempted which indicates thatthe flask had been heated for too long resulting in an uncontrolledpolymerization. This is a consequence of the high viscosity of thesolution of the glassy polymer at low temperatures. Although highmolecular weight was reached, chain-end functionality may be low due tooverheated polymerization solution resulting in solid glassy polymer anda broken stirring rod.

Example 1. Polymerization of Methyl Methacrylate (MMA)

Polymerization of MMA was carried out first using the new ‘feeding’method for ICAR ATRP. The best polymerization conditions were chosenfrom the computer modeling and tested in a 1 liter scale reactor. Thetemperature inside the reactor was followed using a thermocouple with asecond thermocouple located outside the reactor, between the wall of thereactor and the heating mantle to provide additional information of thelevel of temperature control attained in the reaction. The difference intemperature between the two thermocouples can be related to theefficiency of heat transfer in this system. The efficiency of heattransfer may change significantly with viscosity and will affect thecontrol of polymerization.

Another factor which computer modeling does not take into account is therate of diffusion of the radical initiator after feeding into a viscoussolution. The radical initiator should be evenly distributed beforesignificant decomposition occurs. In order to investigate that, atdifferent stages of the polymerization (when solution will becomeprogressively more viscous), a colored dye will be injected and a timeof its distribution will be evaluated (visually and/orspectroscopicaly). The results of this study will provide information onthe distribution of injection sites required for optimal control in alarge scale reactor.

Polymerization of MMA Using the Proposed Method

The results of the computer simulations were used as starting points for10 test reactions. It was determined that an excess of ligand had to beused in order to get a controlled polymerization. Polymerizationsrevealed linear kinetics and molecular weights were close to theoreticalvalues. However, when targeting low DP the PDI's remained quite broad,FIG. 9. Additional reactions were then performed to optimize synthesisof PMMA using the disclosed feeding method. The results and observationsduring the initial experiments indicated that the reason for poorresults, broad PDI, is very low initiation efficiency of DEBMM in theICAR ATRP system, a signal from the initiator was visible on GC traceseven after several hours of reaction. For high DP polymers molecularweights were lower than theoretical values and PDI initially decreasedwith conversion but increased at high conversion, FIG. 10. Anotherobservation was that the polymerization mixture was becoming cloudy withreaction time. This is probably the reason for loss of the control atthe end of most of the polymerization reactions. It was determined thatthe selected ATRP initiator (DEBMM) was mostly responsible for sidereaction and destabilization of the very low concentration of coppercatalyst.

Therefore a more efficient initiator, BrPN, was tested in ICAR ATRP withfeeding of AIBN and good results were obtained.

After performing the first reactions with MMA, the experimental and thesimulated results were compared. Differences can be attributed toeffects of heat transfer, viscosity, initiator diffusion, impurities,and the amount of air in the system. These observations indicate thatthe reactor should be equipped with a mechanical stirrer. In order tofurther reduce problems related to diffusion and heat transfer,reactions can be diluted (with monomer or solvent) and stopped at lowerconversions (unreacted monomers (diluents) can be recovered and reused).Additional experiments were conducted in order to optimize the reactionconditions at this scale with a single source of added initiator. Theparameters that were adjusted include: temperature, targeted DP, feedrate of radical initiator, concentration of reagents, and amount of Cucatalyst.

Example 2. Polymerization of n-Butyl Acrylate

Computer Simulations for Polymerization of n-Butyl Acrylate

A computer model similar to that shown in FIG. 2 was built and thenpolymerization simulations were performed for n-butyl acrylate (nBA).The main goal of the simulations was to find starting conditions forreal polymerization experiments by varying several different parametersin the software; type of radical initiator, degree of polymerization DP,feeding rate of radical initiator.

One of the goals for new polymerization method with controlled feedingof the initiator/activator was to make polymerization reactions as fastas possible and at the same time still have a controlled process. As inthe case of PMMA, evaluation of simulated results for PnBA was based onthese factors and new evaluation scale was introduced. The scale wasslightly different than that for MMA due to relatively faster reactionsfor nBA type monomer.

Relative Control Scale Description

Very good: conversion >99% after less than 6 hours reaction and PDI<1.15and functionality >98%, with linear kinetics.

Good: conversion=95-99% after less than 10 hours reaction orPDI=1.15-1.20 or functionality=95-98%,

Intermed.: conversion=80-95% after less than 20 hour PDI=1.20-1.25 orfunctionality=85-95%,

Poor: conversion <80% after less than 20 hour or PDI >1.25 orfunctionality <85%.

All rates and rate constants were adjusted for each simulatedpolymerization as reported in Table 1 presented below.

TABLE 1 Relative Conv. Time Funct. Exp. control [%] [h] PDI [%] Comments25 Good 99.2 1.7 1.13 99 Induction period was observed 25a Poor 99.2 0.51.38 99 High PDI 25b Very good 99.2 1.2 1.15 99 Very short inductionperiod was observed 26 Good 99.2 3.3 1.14 99 Induction period wasobserved 27 Good 99.2 2.6 1.12 99 Induction period was observed 28 Good99.2 4.8 1.09 99 Induction period was observed 29 Good 99.2 4.3 1.11 99Induction period was observed 30 Intermediate 99.2 7.5 1.08 99 Inductionperiod was observed 31 Good 99.2 4.5 1.07 99 Induction period wasobserved 31a Poor 99.2 0.9 1.38 97 High PDI 32 Intermediate 99.2 11.31.04 99 Induction period was observed 32b Intermediate 99.2 1.4 1.21 98Medium PDI 33 Good 99.2 6.0 1.07 99 Induction period was observed 34Intermediate 99.2 13.4 1.04 99 Induction period was observed 35 Poor45.5 6.0 1.09 99 Slow reaction 36 Intermediate 99.2 18.6 1.04 99Induction period was observed 37 Good 99.2 1.9 1.16 99 Induction periodwas observed 38 Good 99.2 4.1 1.10 99 Induction period was observed 39Good 99.2 2.9 1.18 99 Induction period was observed 40 Good 99.2 5.71.11 99 Induction period was observed 41 Good 99.2 4.2 1.19 99 Inductionperiod was observed 42 Good 99.2 7.8 1.12 99 Induction period wasobserved 43 Good 99.2 4.9 1.09 99 Induction period was observed 44Intermediate 99.2 12.8 1.04 99 Induction period was observed 45 Good99.0 6.0 1.11 98 Induction period was observed 46 Intermediate 99.2 14.91.05 99 Induction period was observed 47 Good 92.4 6.0 1.12 99 Inductionperiod was observed 48 Intermediate 99.2 17.8 1.06 99 Induction periodwas observed

In almost all cases resulting polymers had low PDI, high chain-endfunctionality and molecular weights close to theoretical values. Highpolymerization rates were observed for most of the reactions (even forhigh DP) and that's why most of simulations are rated here as good sincenon-linear kinetics were observed. In conclusion simulations forpolymerization of nBA using new ‘feeding’ method were successful andoptimal conditions were found; e.g. Simulations 25, 25a, (see FIG. 11)26-29, 31, 33, 37-43, 45, 47. Overall, there was not a significantdifference in terms of control over the polymerization when using loweror higher T, different radical initiator or different feeding rate. Asexpected, reactions were faster with V-70, with higher T or fasterfeeding rate. The positive effect of feeding of radical initiator foracrylates is much higher than for MMA or St, discussed below. When nofeeding is applied (simulation 25a), polymerization is uncontrolled fornBA (high PDI), FIG. 1.

Conditions optimized using the computer software simulations were usedin experiments on 1 L scale. Results obtained during these experimentsfor nBA are reported below.

Example 2A. Preparation of PnBA Via Starved Feeding ICAR ATRP

Four of the best polymerization conditions were chosen from the modelingstage and first tested in a 1 liter scale reactor. The experimental setup had one difference in comparison with MMA system; the reactor wasequipped with a cooling coil, needed for safety reasons—as reactionswith acrylates are more exothermic. As discussed in the background, weanticipate much less exothermic effects for the “starved” feedingmethod. The parameters that were adjusted are: temperature, targeted DP,feed rate of radical initiator, concentration of reagents, and amount ofCu catalyst.

Run: 08-006-57

Scale: 1 L reactor

Conditions: nBA/DEBMM/CuBr₂/TPMA/AIBN=2000/1/0.02/0.04/0.04 in bulk(anisole as internal standard), (10 ppm of Cu), T=90° C., time=7.5hours.

The rate of addition of the AIBN solution of 34.5 mg AIBN in 15 ml oftoluene was 2 ml/h, which is equivalent to adding 0.01 eq. AIBN/hcompared to the amount of ATRP initiator added. The initial volume ofliquid in the reactor was 840 ml. After 3 hour and 10 minutes anexothermic reaction was noted in the temperature profile and addition ofAIBN was stopped and cooling water started. Cooling was continued forone minute then stopped. The reaction temperature slowly returned to 90°C. and addition of the AIBN solution was resumed after 4 hours at areduced rate of 1 ml/h and no further exothermic reaction was observed.The reaction was stopped after 7½ hours.

The kinetics of the reaction and GPC results of the experiment are shownin FIG. 12 indicating that the final polymer had a DP of 700 and aM_(n(GPC)) 89,900 with a final PDI of 1.26.

The most critical observation was that the temperature of thepolymerization was well controlled and in contrast to the results shownin FIG. 1 this reaction was not excessively exothermic as a consequenceof the low absolute amount of AIBN added over the initial 3 hour periodand when the instantaneous concentration of initiator exceeded theconcentration of the formed CuBr₂/TPMA catalyst due to terminationreactions the resulting exotherm could be readily controlled by stoppingaddition of initiator. The slower rate of termination at higherconversion resulting from increased viscosity required slower rate ofaddition of AIBN.

Therefore in this example it was determined that the concept of“starved” feeding of an initiator did provide improved control.

Example 2B. Polymerization of nBA

Polymerization conditions from simulation 37 were taken as a startingpoint for run 08-006-194 with feeding of V-70 at 70° C. Polymerizationwas very slow at the beginning (induction period) and after 2 h rate ofpolymerization significantly increased. Conversion reached 96% afteronly 4 hours reaction. This fast polymerization process was not wellcontrolled. Although molecular weights were close to theoretical values,PDI was high (>1.7) and did not decrease with conversion. The inductionwas also clearly visible on every simulation. These results suggest thata significant amount of initiator has to be consumed before there is anincrease in the rate of polymerization. Therefore in run 08-006-195 nBAa higher monomer to initiator ratio (DP=1000) was employed. It can beseen from FIG. 13 that control over the polymerization was significantlyimproved. As in the previous case, the kinetic plot was not linear butmolecular weights were close to theoretical values. GPC traces weremonomodal and shifting with reaction time. Molecular weight distributionof synthesized polymer decreased during the polymerization from PDI=1.78to 1.31. The induction period was around 5 h and after this time astrong exothermic effect was observed as shown in FIG. 14. Temperatureincreased from 70° C. to 110° C. The exothermic effect was controlled bystopping addition of V-70 to the reaction mixture. After stopping theaddition, polymerization stopped as well as any further increase oftemperature inside of the reactor.

This experiment proves that ‘feeding’ method is safe for exothermicpolymerization reactions. The control of the exothermic effect may be ofgreat importance in terms of safety as well as control over molecularweight, PDI and functionality of final polymer material.

Additional examples for polymerization of nBA also targeted a higher DPand a small amount of V-70 was added at the beginning of polymerizationprocess to reduce induction period. Polymerization of nBA with lower DPwas also repeated with higher amount of copper catalyst. In bothreactions a well controlled polymerization was observed.

Example 3. Polymerization of Styrene (St)

The polymerization of styrene via the new ‘feeding’ method for ICAR ATRPwas performed using the same strategy as for MMA monomer. Four of thebest polymerization conditions were chosen from the computer modelingstage and tested in a 1 liter scale reactor. After preliminary results,detailed in Table 2, were obtained additional experiments were performedwith improved conditions.

The parameters which were adjusted are: temperature, targeted DP, feedrate of radical initiator, concentration of reagents, and amount of Cucatalyst.

TABLE 2 Experimental conditions and properties of PSt prepared by ICARATRP with feeding of AIBN or thermal initiation.^(a) AIBN T Cu Feedingrate Time Conv. Run No. [° C.] St In [ppm] CuBr₂ Ligand AIBN [eq./h](min) (%) M_(n, theo) ^(b) M_(n, GPC) M_(w)/M_(n) 08-006-185 120 100 150 0.005 0.1 0.0025 0   60 0.11 1100 1100 1.28 (old result) DEBMM TPMAThermal 120 0.20 2100 1700 1.27 initiation 240 0.36 3700 2800 1.27 5200.47 4900 3500 1.27 640 0.48 5000 3600 1.27 08-006-190 100 100 1 500.005 0.1 0 0.004 40 0.02 200 500 1.35 DEBMM TPMA (3.33 ml/h) 90 0.05500 900 1.28 180 0.12 1300 1400 1.25 300 0.27 2800 3200 1.20 630 0.565600 6100 1.16 08-006-192 100 100 1 50 0.005 0.1 0.005 0.008 30 0.101000 800 1.39 DEBMM TPMA (3.33 ml/h) 90 0.17 1700 1700 1.28 180 0.323300 2700 1.23 300 0.49 5100 4800 1.18 540 0.81 8400 7700 1.1508-006-193 100 1000 1 50 0.05 0.15 0.025 0.008 40 0.02 1600 2300 1.32DEBMM TPMA (3.33 ml/h) 90 0.04 4600 4700 1.19 200 0.10 10600 9200 1.15310 0.16 16600 14700 1.14 540 0.24 24500 20100 1.12 1240 0.25 2640020900 1.12 1300 0.26 27200 23300 1.11 1420 0.37 38100 25200 1.15 16000.46 47500 31900 1.15 1840 0.57 59500 37700 1.18 ^(a)polymerizationswere performed in bulk in 1 L reactor with overall volume of 850 ml andwith 5% of DMF as the internal standard; ^(b)M_(n, theo) = ([M]₀/[In]₀)× conversion.

The polymerization kinetics were followed by measuring the rate ofdisappearance of monomer by gas chromatography (GC) and/or by nuclearmagnetic resonance (NMR). The synthesized polymers will be characterizedby gel permeation chromatography (GPC). Successful polymerization ofmonomer M should result in polymer P(M) with monomodal and narrowmolecular weight distribution (PDI<1.4). Molecular weight of thesynthesized polymers should be close to theoretical values as predictedfrom equation 2:

M_(n,theo)=([M]₀/[R—X]₀)×conversion×M_(monomer).  (2)

Examples for Polymerization of Styrene Using the Proposed Method

The computer model was build and then polymerization simulations wereperformed for styrene (St). Table 2 presents all of the results forpolymerization of St using ICAR ATRP with feeding of AIBN. In experimentWJ-08-008-190 St was polymerized in the presence of DEBMM as initiatorwith 50 ppm of CuBr₂ and excess of TPMA. Polymerization was carried at100° C. and AIBN was fed at 0.004 eq. vs. DEBMM per hour. Polymerizationreached 56% conversion in 10.5 h. Linear kinetics, were observed andmolecular weights were very close to the theoretical values. In thisexperiment PDI decreased during the reaction time from 1.35 to 1.16.Overall, the process was fully controlled.

In the second reaction, WJ-08-006-192, FIG. 15, a higher addition rateof AIBN was applied in order to accelerate rate of polymerization. Inaddition, a small amount of AIBN was added at t=0 to the reactionmixture in order to reduce most of Cu(II) to Cu(I) at the beginningstage of polymerization. Polymerization was almost two times fasterreaching 81% conversion in 9 hour. The kinetic plot has lineardependence and molecular weights are close to theoretical values. GPCtraces are monomodal and are shifting with reaction time. Molecularweight distribution of synthesized polymers decreased duringpolymerization from 1.39 to 1.15. This data proves that process wasfully controlled.

In final reaction reported in Table 2, reaction (WJ-08-006-193),polymerization of St was performed targeting a higher DP. St waspolymerized in the presence of DEBMM as initiator with 50 ppm of CuBr2and excess of TPMA. Polymerization was carried at 100° C. and AIBN wasfed at 0.008 eq. vs. DEBMM per hour. FIG. 16 shows kinetic plot for thisreaction. After 9 h the addition of AIBN was stopped and heating wasturned off. It can be seen from FIG. 16 that the polymerization processstopped immediately after stopping addition of the initiator. Thereactor was allowed to cool down overnight (no cooling system applied)and heated again after 21.6 h up to 110° C. At this time feeding of AIBNwas restarted with the same addition rate. It can be seen from thekinetic plot, FIG. 17 and molecular weights vs. conversion plot FIG. 16,that this reaction was restarted in fully controlled way.

Due to higher temperature in second phase of the reaction the rate ofpolymerization was higher. FIG. 16 also shows temperature inside as wellas outside of the reactor, thermocouples were placed insidepolymerization mixture and on the outer wall of the reactor. Thetemperature profile indicates good heat transfer as the difference intemperature from both thermocouples is similar and does not increase atany time during the reaction.

This set of data proves that the new ‘feeding’ process can be fullyautomated and that ICAR ATRP with controlled feeding can be successfullyapplied in synthesis of PSt with low as well high DP's.

Therefore in one embodiment of the invention we disclose how the rate ofdecomposition of the added free radical initiator is one factorcontrolling the rate of the CRP and the level of control over themolecular weight, molecular weight distribution and chain endfunctionality in the formed (co)polymer.

Another embodiment of the invention discloses that if the temperature ofthe reaction medium moves above the target temperature and the additionof the initiator/reducing agent is terminated, there is no furtherexotherm and, once the temperature drops to the target temperature, thefeeding of the initiator/reducing agent can be started to reinitiate thepolymerization reaction.

Another embodiment of the disclosed process is directed towardscontinuous control over the concentration of the persistent radical in aNMP. In this embodiment the rate of decomposition of the added initiatoris selected to match the rate of radical/radical termination reactionsthat would otherwise build up the concentration of the stable freeradical and reduce the rate of propagation.

A further embodiment of the disclosed process concerns RAFTpolymerizations. In a RAFT polymerization the rate of polymerization iscontrolled by the rate of added initiator. Normally all of the initiatoris added to the reaction at the beginning of the reaction and this couldlead to an increased rate of initiator decomposition if the temperatureof the reaction is not well controlled throughout the polymerizationvessel during each stage of the reaction.

In another embodiment of the invention a photoresponsive initiator isemployed and the rate of radical generation is controlled byintermittent controlled photo-stimulation.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. It is intendedthat the following claims define the scope of the invention and thatmethods and structures within the scope of these claims and theirequivalents be covered thereby.

1. (canceled)
 2. A method of polymerizing unsaturated monomers,comprising: (a) mixing unsaturated monomers with an inactive metalcatalyst, optionally ligand and an initiator having a transferable atom,wherein the inactive metal catalyst is present in the mixture at anamount of less than 250 ppm, on a mass basis relative to the totalmixture; (b) heating the mixture to a reaction temperature; (c) adding afirst portion of a non-activated reducing agent to the system togenerate an activated reducing agent, wherein the non-activated reducingagent has a decomposition activation-dependent tin value of between 30sec. and 30 min. at least one of the reaction conditions; (d) reducingthe inactive metal catalyst with the activated reducing agent to form anactive metal catalyst; (e) transferring the transferable atom with theactive metal catalyst, thereby activating the initiator for unsaturatedmonomer addition; and (f) adding at least a further portion of thenon-activated reducing agent to the mixture to induce furtherpolymerization of the unsaturated monomer; wherein the at least furtherportion is added to the mixture at a point where at least 30 molar %,relative to the amount of unsaturated monomer introduced into themixture, has been polymerized, and wherein at least one polymer producthas a degree of polymerization, with respect to the monomer residuescorresponding to the unsaturated monomer, of at least 20 and the overallmixture has a conversion of at least 60 molar % relative to the amountof unsaturated monomer introduced into the mixture.
 3. A method ofradical polymerization of an unsaturated monomer, comprising: (a)polymerizing an unsaturated monomer in a system comprising an initiator,optionally ligand and a metal catalyst at or above a reactiontemperature; (b) adding at a controlled rate a first amount ofnon-activated reducing agent to the system; and (c) controlling the rateof polymerization of the unsaturated monomer by adding at a controlledrate a further amount of the non-activated reducing agent to the systemat a point where at least 30 molar %, relative to the amount ofunsaturated monomer introduced into the system, has been polymerized;wherein at least one reaction condition is at or above a point suitableto trigger the decomposition of the non-activated reducing agent to forman active reducing agent.
 4. The method of claim 3, wherein thenon-activated reducing agent has an activation-dependent t_(1/2) valueof between 30 sec. and 30 min.
 5. The method of claim 3, wherein the atleast one reaction condition is temperature.
 6. The method of claim 3,wherein the at least one reaction condition includes electromagneticenergy.
 7. The method of claim 3, wherein the initiator is ahalide-substituted alkyl initiator.
 8. The method of claim 3, whereinthe metal catalyst is an inactive metal-halide catalyst.
 9. A method ofmaking a polymer, comprising: (a) preparing a reaction mixturecomprising a radically-polymerizable unsaturated monomer, an initiator,optionally ligand and an inactive metal catalyst in a molar ratio of theunsaturated monomer to the initiator of 25-5000:1 and a molar ratio ofthe catalyst to the initiator of 0.001 to 0.5:1 and the inactive metalcatalyst is present in the mixture at an amount of less than 250 ppm, ona mass basis relative to the total mixture; (b) heating the reactionmixture to a first temperature; (c) disbursing a portion of athermo-activated reducing agent into the heated reaction mixture; (d)allowing a quantity of said portion of the thermo-activated reducingagent to decompose to an activated reducing agent; (e) reducing aportion of the inactive metal catalyst with a portion of the activatedreducing agent to form at least one active metal catalyst; (f)activating one or more of the initiators with the at least one activemetal catalyst to form one or more activated initiators; (g)polymerizing at least one monomer in the presence of one or moreactivated initiators to extend a polymer chain; and (h) repeating steps(c)-(g) while maintaining the temperature at or above a secondtemperature; wherein the first and second temperatures are at or above atemperature wherein the thermo-activated reducing agent has atemperature-dependent t_(1/2) value of between 30 sec. and 30 min. 10.The method of claim 9, wherein the initiator is a halide-substitutedalkyl initiator.
 11. The method of claim 9, wherein the inactive metalcatalyst an inactive metal-halide catalyst.
 12. The method of claim 9,wherein steps (c)-(h) are conducted substantially continuously for aperiod of at least 2 hours.
 13. The method of claim 9, wherein thethermo-activated reducing agent is continuously being disbursed into theheated reaction mixture and the portion is adjusted periodically overthe course of the polymerization reaction, relative to the molarconversion of unsaturated monomer.
 14. The method of claim 9, whereinthe thermo-activated reducing agent is continuously being disbursed intothe heated reaction mixture and the portion is adjusted periodicallyover the time course of the polymerization reaction, relative to theprocess parameters of temperature and viscosity.
 15. The method of claim9, wherein the thermo-activated reducing agent is continuously beingdisbursed into the heated reaction mixture and the portion is adjustedperiodically over the course of the polymerization reaction, relative tothe molar conversion of unsaturated monomer, over an interval of time,wherein the interval of time is greater than 3 minutes.
 16. The methodof claim 9, wherein the non-activated reducing agent is not added untilat least 60 molar % conversion of the unsaturated monomer is achieved,relative to the molar amount of unsaturated monomer.
 17. The method ofclaim 9, wherein said second temperature is at least 10 degrees hotterthan said first temperature.
 18. The method of claim 9, wherein thepolymerization reaction is an ARGET ATRP reaction.
 19. The method ofclaim 9, wherein the polymerization reaction is an ICAR ARGET ATRPreaction.
 20. The method of claim 9, wherein the polymerization reactionis conducted at a temperature within 15 degrees celsius below theboiling point of the unsaturated monomer.